Brain-derived neurotrophic factor

Brain-Derived Neurotrophic Factor (BDNF) Role in Cannabinoid-Mediated Neurogenesis

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The adult mammalian brain can produce new neurons in a process called adult neurogenesis, which occurs mainly in the subventricular zone (SVZ) and in the hippocampal dentate gyrus (DG). Brain-derived neurotrophic factor (BDNF) signaling and cannabinoid type 1 and 2 receptors (CB1R and CB2R) have been shown to independently modulate neurogenesis, but how they may interact is unknown. We now used SVZ and DG neurosphere cultures from early (P1-3) postnatal rats to study the CB1R and CB2R crosstalk with BDNF in modulating neurogenesis. BDNF promoted an increase in SVZ and DG stemness and cell proliferation, an effect blocked by a CB2R selective antagonist. CB2R selective activation promoted an increase in DG multipotency, which was inhibited by the presence of a BDNF scavenger. CB1R activation induced an increase in SVZ and DG cell proliferation, being both effects dependent on BDNF. Furthermore, SVZ and DG neuronal differentiation was facilitated by CB1R and/or CB2R activation and this effect was blocked by sequestering endogenous BDNF. Conversely, BDNF promoted neuronal differentiation, an effect abrogated in SVZ cells by CB1R or CB2R blockade while in DG cells was inhibited by CB2R blockade. We conclude that endogenous BDNF is crucial for the cannabinoid-mediated effects on SVZ and DG neurogenesis. On the other hand, cannabinoid receptor signaling is also determinant for BDNF actions upon neurogenesis. These findings provide support for an interaction between BDNF and endocannabinoid signaling to control neurogenesis at distinct levels, further contributing to highlight novel mechanisms in the emerging field of brain repair.

Introduction

Constitutive neurogenesis occurs in the adult mammalian brain where NSPC are able to differentiate into three neural lineages, neurons, astrocytes and oligodendrocytes (Gage, 2000; Gross, 2000). These multipotent cells exhibit properties of self-renewal and cell proliferation that allow the maintenance of their own pool (Ma et al., 2009). Neurogenesis occurs mainly in two brain areas, the subventricular zone (SVZ) and the subgranular zone (SGZ) within the DG of the hippocampus. These regions are packed with NSPC that originate neuroblasts which migrate toward their final destinations, where they differentiate into mature neurons and are integrated into the neuronal circuitry (Lledo et al., 2006; Zhao et al., 2008; Ming and Song, 2011).

Adult neurogenesis and the neurogenic niches are highly regulated by several factors (intrinsic and extrinsic factors) that control the NSPC rates of proliferation, lineage differentiation, migration, maturation and survival (Ming and Song, 2011). Knowing and understanding the actions of these factors will further contribute to develop new therapeutic strategies useful for brain repair and regeneration. However, there is still a lack of knowledge regarding the key factors that regulate each step of postnatal neurogenesis.

The role of neurotrophins and, in particular, brain-derived neurotrophic factor (BDNF) in adult neurogenesis has been the subject of many studies (Henry et al., 2007; Chan et al., 2008; Vilar and Mira, 2016). BDNF is expressed in both SVZ and SGZ neurogenic niches (Galvão et al., 2008; Li et al., 2008) but its precise role in adult neurogenesis is still not consensual. In fact, some studies suggest that BDNF is important to positively regulate DG cell proliferation and survival (Chan et al., 2008; Li et al., 2008) while others report no BDNF-induced changes in DG neurogenesis (Choi et al., 2009). In SVZ, most studies depict that BDNF does not promote any significant changes in cell proliferation and survival (Henry et al., 2007; Galvão et al., 2008), despite having a role in the migration of SVZ-derived cells (Snapyan et al., 2009; Bagley and Belluscio, 2010). Despite the available contradictory data, BDNF, through TrkB signaling, was shown to have an essential role in the regulation of dendritic complexity as well as synaptic formation, maturation and plasticity of newborn neurons (Chan et al., 2008; Gao et al., 2009; Wang et al., 2015).

Besides expressing BDNF, NSPC present in the neurogenic niches were shown to express all the elements of the endocannabinoid system (Aguado et al., 2005; Arévalo-Martín et al., 2007), including the main cannabinoid receptors type 1 (CB1R) and type 2 (CB2R) receptors (Rodrigues et al., 2017). They are both present in the CNS, although CB2R expression is relatively higher in the immune system (Galve-Roperh et al., 2007). In recent years, the role of cannabinoids in neurogenesis has been of particular interest given their multiplicity of neuromodulatory functions (Mechoulam and Parker, 2013). Cannabinoid receptors modulate adult neurogenesis by acting at distinct neurogenic phases (Prenderville et al., 2015). Importantly, activation of type 1 (Xapelli et al., 2013) or type 2 cannabinoid receptors (Palazuelos et al., 2006) by selective agonists was found to regulate cell proliferation, neuronal differentiation and maturation (Rodrigues et al., 2017).

Several studies have provided molecular and functional evidence for a crosstalk between BDNF and endocannabinoid signaling (Maison et al., 2009; Zhao et al., 2015). Synergism between BDNF and CB1R has been observed both in vitro and in vivo (De Chiara et al., 2010; Galve-Roperh et al., 2013). In particular, BDNF was shown to regulate striatal CB1R actions (De Chiara et al., 2010). Moreover, evidence for BDNF-TrkB signaling interplay with CB1R has been shown to trigger endocannabinoid release at cortical excitatory synapses (Yeh et al., 2017). Importantly, genetic deletion of CB1R was shown to promote a decrease in BDNF expression (Aso et al., 2008) while induction of BDNF expression contributed to the protective effect of CB1R activity against excitotoxicity (Marsicano, 2003; Khaspekov et al., 2004). Moreover, CB1R activity can enhance TrkB signaling partly by activating MAP kinase/ERK kinase pathways (Derkinderen et al., 2003) but also by directly transactivating the TrkB receptors (Berghuis et al., 2005). Δ9-THC, the principal active component of cannabis, was shown to promote upregulation of BDNF expression (Butovsky et al., 2005) whereas increased levels of BDNF were shown to rescue the cognitive deficits promoted by Δ9-THC administration (Segal-Gavish et al., 2017). Interestingly, clinical data suggests that acute and chronic intermittent exposure to Δ9-THC alters BDNF serum levels in humans (D’Souza et al., 2009).

Given the evidence that BDNF and cannabinoid signaling can affect neurogenesis as well as the fact that BDNF may interact with cannabinoid receptors, we hypothesized that cannabinoid receptors could act together with BDNF signaling to fine-tune neurogenesis. We show for the first time that endogenous BDNF is crucial for the cannabinoid-mediated effects on SVZ and DG neurogenesis to happen. Moreover, we demonstrate that CB2R has a preponderant role in regulating some of the BDNF actions on neurogenesis. Taken together, our results suggest an important crosstalk between BDNF and cannabinoid signaling to modulate postnatal neurogenesis.

Discussion

The present work reveals a yet not described interaction between BDNF and cannabinoid receptors (CB1R and CB2R) responsible to modulate several aspects of SVZ and DG postnatal neurogenesis. BDNF was shown to be an important modulator of SVZ and DG postnatal neurogenesis, its actions being under control of cannabinoid receptors. The relevance of each cannabinoid receptor to control the action of BDNF upon neurogenesis is different in the two neurogenic niches. While CB2R has a preponderant role in modulating BDNF actions on DG, BDNF-mediated SVZ postnatal neurogenesis is modulated by both CB1R and CB2R. A constant and clear finding in both neurogenic niches is that BDNF is required for cannabinoid actions to occur. It thus appears that a reciprocal cross-talk between cannabinoids and BDNF exist to modulate postnatal neurogenesis.

BDNF is a neurotrophin important in the regulation of several neuronal processes such as neuronal branching, dendrite formation and synaptic plasticity (Dijkhuizen and Ghosh, 2005; Gómez-Palacio-Schjetnan and Escobar, 2013). In line with this evidence, several studies have shed light on the actions of BDNF in the survival and differentiation of newborn neurons (Benraiss et al., 2001; Henry et al., 2007; Chan et al., 2008; Snapyan et al., 2009). Our findings now demonstrate that BDNF is able to affect early steps of postnatal neurogenesis, such as cell-fate, cell proliferation and neuronal differentiation of SVZ and DG cultures. We observed that BDNF promoted self-renewal of SVZ- and DG-derived cells as observed by an increase in self-renewal divisions, i.e., an increase in the percentage of Sox2+/+ cell-pairs. BDNF-CBR crosstalk has been reported to control several processes at the synaptic level (Zhao and Levine, 2014; Zhong et al., 2015) and we now extended these findings toward very early stages of postnatal neurogenesis. Interestingly, the increase in the SVZ and DG pool of stem/progenitor cells mediated by BDNF was fully abolished in the presence of CB2R antagonist but not CB1R antagonist. An exception is the influence of BDNF upon SVZ cell proliferation, which is not affected by CB1R or CB2R selective antagonism. In what concerns neuronal differentiation, both CB1R and CB2R are required for BDNF actions on SVZ whereas at the DG, only CB2R seem to affect BDNF-promoted neuronal differentiation. Overall, cannabinoid receptor blockade appears to influence more BDNF-induced actions upon early stages of DG neurogenesis in comparison to SVZ, highlighting the fact that cannabinoids distinctly modulate the effects promoted by BDNF in SVZ and DG neurogenesis.

It was previously known that the endocannabinoid system and cannabinoid receptors are important modulators of several stages of neurogenesis (Palazuelos et al., 2012; Xapelli et al., 2013; Prenderville et al., 2015; Rodrigues et al., 2017). In accordance with our previous data, SVZ and DG cells were differently affected by the same cannabinoid pharmacological treatments (Rodrigues et al., 2017). Considering cell fate, we observed that selective activation of CB2R activation promotes self-renewal of DG cells, but not of SVZ cells. This is consistent with several pieces of evidence showing a regulation of cell fate promoted by the activation of several signaling pathways [such as mitogen-activated protein kinase (MAPK) family (ERK, JNK and p38) and the phosphoinositide-3 kinase (PI3K)/AKT pathways] triggered by CBR activation (Molina-Holgado et al., 2007; Gomez et al., 2010; Soltys et al., 2010; Compagnucci et al., 2013).

On the other hand, our results reveal, for the first time, a role of cannabinoid receptors (CB1R and CB2R) in regulating DG cell commitment.

Considering cell proliferation, it is promoted by CB1R but not CB2 at SVZ, while at DG cell proliferation was only induced by co-activation of CB1R and CB2R. These results are in accordance with previous reports that have shown an increase in SVZ cell proliferation promoted by CB1R selective activation (Trazzi et al., 2010; Xapelli et al., 2013) and an increase in DG cell proliferation triggered by CB1R/CB2R non-selective activation (Aguado et al., 2005; Rodrigues et al., 2017). Importantly, while we also detected an effect with the non-selective CB1R/CB2R agonists, none of the selective agonists when applied in the absence of the other agonist were effective to promote cell proliferation in the DG, highlighting the need of caution while interpreting negative results with each of those agonists separately.

Regarding neuronal differentiation, our data indicate that in SVZ and DG neurogenic niches both subtypes of cannabinoid receptors are able to promote neuronal differentiation. These data are in accordance with previous reports in which cannabinoid receptor activation enhanced neuronal differentiation of NSPC by CB1R- (Compagnucci et al., 2013) or CB2R-dependent (Avraham et al., 2014) mechanisms.

The most important finding in the present work is that most of the cannabinoid-induced effects upon cell proliferation and neuronal differentiation depend on the presence of BDNF, suggesting the existence of a BDNF-endocannabinoid feedback loop responsible for regulating these processes. Previous reports have shed light on the existence of a putative interaction between BDNF and cannabinoid receptors (Howlett et al., 2010), but none focused upon neurogenesis. De Chiara et al. (2010) have identified a novel mechanism by which BDNF mediates the regulation of striatal CB1R function. Moreover, others have suggested that BDNF can regulate neuronal sensitivity to endocannabinoids through a positive feedback loop important for the regulation of neuronal survival (Maison et al., 2009). Evidence also shows the involvement of BDNF in the actions mediated by cannabinoids against excitotoxicity (Khaspekov et al., 2004), in synaptic transmission and plasticity (Klug and van den Buuse, 2013; Zhao et al., 2015; Yeh et al., 2017) and in several behavioral outputs (Aso et al., 2008; Bennett et al., 2017). Previous animal studies have shown that acute (Derkinderen et al., 2003) and chronic (Butovsky et al., 2005) Δ9-THC (major psychoactive constituent of cannabis; CB1R and CB2R agonist) administration is associated with an increase in BDNF gene expression. Moreover, it was shown that overexpression of BDNF is able to rescue cognitive deficits promoted by Δ9-THC administration in a mouse model of schizophrenia (Segal-Gavish et al., 2017). In human studies it was found that Δ9-THC increased serum BDNF levels in healthy controls, but not in chronic cannabis users (D’Souza et al., 2009). In fact, cyclic AMP response element-binding protein (CREB) may be the common linking element because it is an important regulator of BDNF-induced gene expression (Finkbeiner et al., 1997), and has been reported to control several steps of the neurogenic process in the adult hippocampus (Nakagawa et al., 2002) and SVZ (Giachino et al., 2005). Consistently, cannabinoids have been shown to induce CREB phosphorylation (Isokawa, 2009) and also to promote changes in BDNF and CREB gene expression (Grigorenko et al., 2002). In addition, the work done by Berghuis et al. (2005) showed that endocannabinoids stimulate TrkB receptor phosphorylation during interneuron morphogenesis. Most importantly, in the same study, the authors observed by co-immunoprecipitation the formation of heteromeric complexes in PC12 cells expressing TrkB receptors and CB1R (Berghuis et al., 2005). Our study brings new and relevant information on the interaction between cannabinoid receptors and BDNF in controlling SVZ and DG neurogenesis, and clearly highlights that this interaction is reciprocal. In fact, neurogenesis promoted by cannabinoid receptor activation depends on the presence of endogenous BDNF, while the effects mediated by BDNF upon neurogenesis are directly regulated by modulation of CB1R or CB2R.

Although our study is based on an in vitro approach, the neurosphere assay, it represents a highly relevant model. In vitro systems of NSPC allow an easier access and better control of experimental variables as well as a thorough analysis of mechanisms happening at cellular and molecular level providing useful information to be further validated in vivo (Singec et al., 2006). Moreover, the heterogeneous composition of the NSPC grown in neurospheres is extremely relevant because it holds some of the features, such as close contact with neighboring cells (newly generated neuroblasts, astrocytes and oligodendrocytes), that resemble those of the physiological niche (Casarosa et al., 2014). These well-established advantages (Aguado et al., 2007; Agasse et al., 2008; Azari et al., 2010) are the reason why we have used this in vitro approach to study the intrinsic properties of NSPC and to understand the interaction between BDNF and cannabinoids in modulating neurogenesis. It is, however, important to mention that the mechanisms governing the regulation of neurosphere dynamics might be different from the ones regulating in vivo adult neurogenesis (Casarosa et al., 2014). Indeed, further in vivo studies will be required to comprehensively understand the role of BDNF in regulating the actions of cannabinoid receptors on postnatal neurogenesis.

Taken together, our data highlight a novel level of complexity for the regulatory mechanisms involved in NSPC dynamics, which involve the interplay of multiple signaling cues, and where BDNF and cannabinoids may play a relevant role. Further in vitro studies are required to detail the molecular mechanisms involved, as well as in vivo studies to determine the functional consequences of the BDNF/cannabinoid crosstalk to control neurogenesis. Nevertheless, our study provides evidence for the need of integrative strategies whenever focusing on NSPC for brain repair.

How BDNF Keeps Your Brain Healthy and How To Boost Yours

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brain support

Forgetting your car keys or not remembering where you parked the car. Blanking on a name when making introductions. We all experience these forgetful moments. They unnerve us and maybe they even strike fear in our hearts as we wonder if something sinister could be responsible. For most people, these blips are just that. For others, the news may be less reassuring. But the positive message for all of us is that there are things we can do right now to help lower the risk of neurological problems down the road. One of the most important may be to increase our brain-derived neurotrophic factor (BDNF), to help improve brain function and lower the risk of neurodegenerative disease. How to boost yours? Start here:

What is BDNF?

A relatively new discovery, BDNF is a naturally occurring protein in the brain that helps keeps your billions of brain cells thriving and healthy. It helps grow new cells and cell pathways, while strengthening the brain and nerve cells you already have, protecting them from damage caused by stress.

Why does BDNF matter?

If you care about your healthspan – the amount of healthy life you pack into your years, BDNF matters – a lot! Maintaining high levels helps your brain age more slowly, improves learning and memory, protects you from Alzheimer’s disease, and works as a natural antidepressant with the ability to reverse chronic anxiety and depression. By keeping your BDNF levels high, you’ll help your brain stave off age-related shrinkage, fight off neurological problems – Alzheimer’s sufferers tend to have extremely low levels – and even improve your sleep. The more of it you have working for you over the course of your life, the better your brain will work for longer. 

So, what robs your body of BDNF?

On the food front, BDNF-robbers include the classic dietary demons of sugar and processed foods, just in case you needed one more reason to strenuously avoid both. Sugar has long been linked with cognitive decline in humans, and animal studies have shown a direct connection with sugar consumption and reduced BDNF production – not a lot of good news there. My advice? Ditch the stuff, no exceptions. And, if you must sweeten, use a very light hand and opt for healthier alternatives like raw stevia or monkfruit. 

When it comes to lifestyle habits, you can tank your BDNF levels simply by not watching out for the classic, all-too-common health-eroders: chronic stress, exhaustion, and social isolation will all take bites out of your BDNF. Unwinding with cannabis or cocktails? You might want to dial those two down a good bit too. Though THC can boost BDNF levels in occasional cannabis users, low BDNF levels are common in both habitual cannabis smokers and heavy drinkers. 

Got inflammation? Wrestling with obesity and metabolic issues? They’re all associated not only with poor overall health but also with lower BDNF levels, so get to work on turning those around too – preferably, as soon as possible.

What can I do to increase BDNF? 

BDNF is stimulated by any number of the positive habits and lifestyle tweaks I recommend to my patients every day, including:

  • Frequent movement – throughout the day, even just a few minutes at a time if that’s all you can spare, but shoot for at least 30 minutes a day, and check out my 10 move more tips for easy ways to weave more movement into your day 
  • A regular meditation practice – while stress decreases BDNF, meditation helps increase it, while helping you center and calm your mind
  • A simple yoga practice – making time to de-stress regularly is essential to keeping BDNF levels high –  and yoga is an excellent stress-busting way to top off your BDNF tank
  • Plenty of quality rest – better sleep, particularly deep sleep, equals more BDNF release, so work on getting your sleep habits into a restful, 7-8 hours nightly, restorative groove. To re-train yourself to sleep like a baby, try my 11 ways to win at sleep
  • Intermittent fasting – or shortening your daily eating window – as in, eating breakfast late and dinner early, vs. all-day grazing – helps give your body time to rest and repair, as well as tame inflammation which left untamed can decrease BDNF levels big time. To begin an intermittent fasting or time-restricted eating routine, try these how-to tips
  • Social connection – social isolation is a sure-fire route to loneliness, depression, and anxiety, all of which suppress BDNF. Challenging as it may be to connect with others these days, making the effort pays big BDNF dividends for your brain. To re-socialize yourself, check out my tips on how to engage and deepen bonds with others in spite of the current limitations – your long-term brain health depends on it! 
  • Responsible sun exposure – as in, a little regular time in the sun, exposing your skin but stopping before you turn pink, and absolutely no burning. To do it right, try these sensible sunshine exposuretips

Another no-brainer, super easy-to-incorporate way to boost your BDNF? Drink a daily cup or two of green tea, ideally, one that’s certified organic, non-GMO, and third party tested for heavy metals like lead. Though China is among the world’s largest producers, in general, many of the best, healthiest green teas hail from Japan and Sri Lanka.

Are there foods that can help increase BDNF?

You can also help stimulate BDNF with a number of tasty foods, beverages, and spices. Among my favorite, always-in-the-pantry BDNF-boosting big guns that everyone should stock the larder with:

  1. Almonds – raw, unroasted, unblanched organic almonds are rich in polyphenols, which are great for BDNF levels
  2. Avocados –rich in antioxidants and polyphenols, creamy and delicious too!
  3. Berries –organic red raspberries, strawberries, and blackberries
  4. Blueberries – particularly wild blueberries, and always organic
  5. Coffee – but to increase BDNF, be sure to choose your brew wisely, looking for certified organic, non-GMO, sustainably farmed, and/or shade grown, Fair Trade and free of toxins, pesticides, and heavy metals
  6. Eggs – look for pasture-raised eggs from healthy animals for the most omega-3 and the biggest BDNF boost 
  7. Extra Virgin Olive Oil (EVOO) – ideally, cold pressed and stored in dark bottles. (For EVOO buying tips, click here.)
  8. Extra Dark Chocolate – while 70% or above is great, going even higher to 90 or 100% is even better when it comes to boosting benefits
  9. Fish – particularly the ones known as wild caught ‘fatty fish,’ as in anchovies, herring, salmon and sardines, which are loaded with omega-3s which helps boost BDNF
  10. Green tea – as mentioned above
  11. Olives – a pretty close-to-perfect food that’s rich in polyphenols, which is good news for your BDNF levels. To buy the best, check out my buy-like-a-pro  tips
  12. Turmeric – loaded with BDNF-boosting polyphenols, and even more powerful when teamed with a bit of fat and black pepper.

In short, whole, unprocessed foods that are rich in polyphenols will help keep your BDNF levels high. If you’re paying attention to eating right, you’re already getting a fair number of them. My advice, keep up the good work, but expand your repertoire and don’t get stuck eating the same five things all the time. Keep changing it up, branching out to get the widest variety of polys on your plate to amp up your BDNF game.

Can supplements boost BDNF?

You can also stimulate BDNF with certain supplements. One is coffee fruit extract, which is made from the berry of the coffee plant. It delivers not only polyphenols (antioxidant-rich micronutrients) but also a brain-supporting chemical called procyanidin. Other supplements, such as curcumin, omega-3 fatty acids (which you can get by taking fish oil), resveratrol and magnesium will also help boost BDNF.  

Boost BDNF right now – with your feet.

If you do nothing else, remember this: you can make your brain bigger and stronger, and lower the risk of memory loss simply by walking more. Turns out, when we walk, our brains actually release BDNF – often referred to as Miracle Gro for the brain. So, lace up your walking shoes and reap the benefits! When you’re ready to take things a step further, add some resistance training and high-intensity interval training for an extra BDNF boost.

How Exercise Makes Your Brain Grow

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Can exercise help boost your cognitive faculties? Researchers increasingly say the answer is a resounding yes. Recent research reveals that exercise promotes a process now known as neurogenesis, i.e. your brain’s ability to adapt and grow new brain cells, regardless of your age.

Regular Exercise

Story at-a-glance –

  • Recent research reveals that exercise promotes a process known as neurogenesis, i.e. your brain’s ability to adapt and grow new brain cells, regardless of your age
  • During exercise, nerve cells release proteins that stimulate the production of brain-derived neurotrophic factor or BDNF, which in turn helps preserve existing brain cells and stimulates the growth of new neurons
  • There’s compelling evidence showing that exercise produces large cognitive gains and helps fight dementia
  • BDNF is also expressed in your neuro-muscular system where it helps protect against age-related muscle atrophy. So BDNF is actively involved in the preservation and rejuvenation of both your muscles and your brain
  • Workouts using nothing but your own body weight are an efficient way to get fit. You can even fulfill the requirements for a high intensity exercise using nothing more than your own body weight, a chair, and a wall

As reported by Forbes Magazine:1

“Not only has research discovered that we can foster new brain cell growth through exercise, but it may eventually be possible to ‘bottle’ that benefit in prescription medication.

The hippocampus, a brain area closely linked to learning and memory, is especially receptive to new neuron growth in response to endurance exercise. Exactly how and why this happens wasn’t well understood until recently.

Research has discovered that exercise stimulates the production of a protein called FNDC5… Over time, FNDC5 stimulates the production of another protein in the brain called Brain Derived Neurotrophic Factor (BDNF), which in turns stimulates the growth of new nerves and synapses… and also preserves the survival of existing brain cells.”

In essence, physical activity produces biochemical changes that strengthen and renew not only your body but also your brain—particularly areas associated with memory and learning.

Researchers Aim to Bottle Exercise Benefits…

Researchers at Harvard Medical School now believe they may be able to recreate the benefits of exercise by putting this protein, FNDC5, into a pill. Bruce Spiegelman, PhD, told Forbes:

 “What is exciting is that a natural substance can be given in the bloodstream that can mimic some of the effects of endurance exercise on the brain.”

They believe such a drug might be useful for those experiencing cognitive decline, including those with early-stage Alzheimer’s and Parkinson’s disease. So far, the hypothesis has only been tested on animals however.

In a recent study published in the journal Cell,2 the researchers successfully increased BDNF in the brains of mice by piggybacking FNDC5 molecules on a virus. According to the authors:

“Perhaps the most exciting result overall is that peripheral delivery of FNDC5 with adenoviral vectors (i.e. a virus) is sufficient to induce central expression of BDNF and other genes with potential neuroprotective functions or those involved in learning and memory.”

Personally, I don’t believe you can fool your body in the long term. It’s important to realize that while a pill may be able to mimic a specific biological effect that exercise produces, such as increasing production of a specific protein or chemical, it will never provide you with ALL the health effects exercise provides, which go far beyond any one specific effect.

Exercise has countless effects on your body — not only on your muscle fibers and brain, but also on your immune system, your ability to fight cancer and much more. To “mimic” all of these benefits, you would literally need handfuls of different pills — and even then they could never reproduce the synergistic benefits that exercise has on your body and mind.

For example, besides boosting memory and learning, regular exercise is also one of the “secret weapons” to overcoming depression. It does this quite effectively by normalizing insulin resistance and boosting natural “feel good” hormones and neurotransmitters associated with mood control in your brain.

Earlier this summer, Princeton University researchers reported3 that physical exercise also helps you combat anxiety by making your brain more resilient during times of stress.

You Cannot Fool Your Body in the Long Run

While actual physical activity can offer you dozens of health benefits, a pill might only be able to recreate one at a time. Besides losing out on the synergistic benefits, taking a pill versus engaging in physical activity will also cost you financially and physically, as there might be unforeseen adverse side effects of the drug to contend with.

All in all, you’re FAR better off just getting physically active. To get the most out of your workouts, I recommend a comprehensive program that includes Peak Fitness high-intensity exercise, strength training, stretching, and core work.

Non-exercise activity and movement is also critical for optimal health, as explained by Dr. Joan Vernikos. Sitting for extended periods of time is actually an independent risk factor for poor health and premature death. Even if you exercise regularly and are fit, uninterruptedly sitting for a great percentage of the time increases your risk of dying prematurely.

Simply standing up, a minimum of 30 times a day, is a powerful antidote to long periods of sitting and is, surprisingly enough, more effective than walking. The good news is that there are virtually unlimited opportunities for movement throughout the day, from doing housework or gardening, to cooking and even just standing up every 10 minutes.

Your Brain Health Is Directly Related to Exercise

That said, let’s look at some of the beneficial effects exercise can have on your brain. According to John J. Ratey, a psychiatrist who wrote the book Spark: The Revolutionary New Science of Exercise and the Brain, there’s overwhelming evidence that exercise produces large cognitive gains and helps fight dementia. Besides triggering the release of BDNF, exercise also protects your brain by:

  • Increasing production of nerve-protecting compounds
  • Improving and increasing blood flow to your brain
  • Improving development and survival of neurons
  • Altering the way damaging proteins reside inside your brain, which appears to slow the development of Alzheimer’s disease. In animal studies, significantly fewer damaging plaques and fewer bits of beta-amyloid peptides, associated with Alzheimer’s, were found in mice that exercised

Ideally, you’d want to make exercise a regular part of your life from as early on as possible. But it’s never too late to start. Even seniors who take up a fitness regimen can improve their cognitive function.

For example, a team at the University of Edinburgh followed more than 600 people, starting at age 70, who kept detailed logs of their daily physical, mental and social habits. Three years later, their brains were imaged for age-related changes, such as brain shrinkage and damage to the white matter, which is considered the “wiring” of your brain’s communication system. Not surprisingly, seniors who engaged in the most physical exercise showed the least amount of brain shrinkage.4

Similarly, Kirk Erickson, PhD of the University of Pittsburgh, found that adults aged 60 to 80 walking moderately (just 30 to 45 minutes, three days per week for one year) increased the volume of their hippocampus by two percent. The hippocampus is a region of your brain important for memory. Erickson told WebMD:5

“Generally in this age range, people are losing one to three percent per year of hippocampal volume. The changes in the size of the hippocampus were correlated with changes in the blood levels of the brain-derived neurotrophic factor (BDNF).”

Erickson also found higher fitness levels associated with a larger prefrontal cortex. He called exercise “one of the most promising nonpharmaceutical treatments to improve brain health.” The most important message from studies like these is that mental decline is NOT inevitable! And exercise is as good for your brain as it is for the rest of your body.

Fasting Can Also Trigger Brain Rejuvenation

Growing evidence indicates that fasting and exercise trigger similar genes and growth factors that recycle and rejuvenate both your brain and muscle tissues. These growth factors include BDNF, as previously mentioned, as well as muscle regulatory factors, or MRFs. These growth factors signal brain stem cells and muscle satellite cells to convert into new neurons and new muscle cells respectively.

Interestingly enough, BDNF also expresses itself in the neuro-muscular system where it protects neuro-motors from degradation. (The neuromotor is the most critical element in your muscle. Without the neuromotor, your muscle is like an engine without ignition. Neuro-motor degradation is part of the process that explains age-related muscle atrophy.)

So BDNF is actively involved in both your muscles and your brain, and this cross-connection, if you will, appears to be a major part of the explanation for why a physical workout can have such a beneficial impact on your brain tissue. It, quite literally, helps prevent, and even reverse, brain decay as much as it prevents and reverses age-related muscle decay.

This also helps explain why exercise while fasting can help keep your brain, neuro-motors, and muscle fibers biologically young. For more information on how to incorporate intermittent fasting into your exercise routine for maximum benefits, please see this previous article. Sugar suppresses BDNF, which also helps explain why a low-sugar diet in combination with regular exercise is so effective for protecting memory and staving off depression.

Almost Anyone Can Improve Their Fitness Without Joining a Gym

In related fitness news, forgoing expensive exercise equipment and focusing on pushing, pulling and lifting your own body weight is becoming a popular alternative that is suitable for most people, regardless of age or fitness level. According to Bret Contreras,6 author of Bodyweight Strength Training Anatomy:

“If more people knew you could get a good physique using your body as a bar bell, they could take matters into their own hands. Find things in the environment: a table to get underneath, hold on to the sides of and then pull the body upward; a rafter for a pull-up. To work your glutes (buttocks muscles), all you need is a couch. It doesn’t have to be intimidating. You could do a 20-minute workout three times a week and have an incredible physique, so long as you push hard and keep challenging yourself.”

Adaptability is a major benefit of body weight exercises: It’s adjustable to almost anyone, from the least fit to the professional athlete. Just learn the basics and try different approaches until you find what works best for you. In the video below, Jill Rodriguez, one of the personal trainers at Mercola.com, demonstrates some basic body weight exercises, and how to add levels of difficulty as you go along.

 

You can do these exercises just about anywhere… at home, outdoors, or in a gym. You can even fulfill the requirements for a high intensity exercise using nothing more than your own body weight, a chair, and a wall! This program is described in my previous article, “The Scientific 7-Minute Workout.” As the title implies, this science-backed routine only requires a seven minute investment, as the program calls for as little as 10- to 15-seconds of rest between each 30-second exercise, which should be performed in rapid succession.

Need a Portable Fitness Routine? There’s an App for That…

In today’s world, you have plenty of technological allies in fitness. With prices ranging from free to $3.99, a previous article brings you information about six bodyweight apps for your iPad or phone. One helps you work out your own customized workout for your skill and fitness level. Another can keep you body challenged. Other non-bodyweight training apps help you track your progress in jogging or running, keep track of your workouts, or calculate heart rate with a range of tools to keep you on track. These apps let you bring your own personal trainer along on every workout, no matter where you are.

For Total Body-Mind Health, Adopt a Well-Rounded Fitness Program

Ideally, you’ll want to strive for a varied and well-rounded fitness program that incorporates a wide variety of exercises. As a general rule, as soon as an exercise becomes easy to complete, you need to increase the intensity and/or try another exercise to keep challenging your body.

Additionally, as I mentioned earlier, more recent research has really turned the spotlight on the importance of non-exercise movement. Truly, the key to health is to remain as active as you can, all day long, but that doesn’t mean you train like an athlete for hours a day. It simply means, whenever you have a chance to move and stretch your body in the course of going about your day—do it!

And the more frequently, the better. Everything from standing up, to reaching for an item on a tall shelf, to weeding in your garden and walking from one room to another, and even doing dishes count. In short, it’s physical movement, period, that promotes health benefits by the interaction your body gets with gravity. To learn more about this important aspect of health, please see this previous article. That said, I recommend incorporating the following types of exercise into your program:

    1. Interval (Anaerobic) Training: This is when you alternate short bursts of high-intensity exercise with gentle recovery periods.
    2. Strength Training: Rounding out your exercise program with a 1-set strength training routine will ensure that you’re really optimizing the possible health benefits of a regular exercise program. You can also “up” the intensity by slowing it down. For more information about using super slow weight training as a form of high intensity interval exercise, please see my interview with Dr. Doug McGuff.
    3. Stand Up Every 10 Minutes. This is not intuitively obvious but emerging evidence clearly shows that even highly fit people who exceed the expert exercise recommendations are headed for premature death if they sit for long periods of time. My interview with NASA scientist Dr. Joan Vernikos goes into great detail why this is so, and what you can do about it. Personally, I usually set my timer for 10 minutes while sitting, and then stand up and do one legged squats, jump squats or lunges when the timer goes off. The key is that you need to be moving all day long, even in non-exercise activities.
    4. Core Exercises: Your body has 29 core muscles located mostly in your back, abdomen and pelvis. This group of muscles provides the foundation for movement throughout your entire body, and strengthening them can help protect and support your back, make your spine and body less prone to injury and help you gain greater balance and stability.

Foundation Training, created by Dr. Eric Goodman, is an integral first step of a larger program he calls “Modern Moveology,” which consists of a catalog of exercises. Postural exercises such as those taught in Foundation Training are critical not just for properly supporting your frame during daily activities, they also retrain your body so you can safely perform high-intensity exercises without risking injury.

Exercise programs like Pilates and yoga are also great for strengthening your core muscles, as are specific exercises you can learn from a personal trainer.

  1. Stretching: My favorite type of stretching is active isolated stretches developed by Aaron Mattes. With Active Isolated Stretching, you hold each stretch for only two seconds, which works with your body’s natural physiological makeup to improve circulation and increase the elasticity of muscle joints. This technique also allows your body to repair itself and prepare for daily activity. You can also use devices like the Power Plate to help you stretch.

How Exercise Can Moderate Brain Damage Caused by Drinking.

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brain-exercise

 

It’s well known that chronic, heavy drinking damages your brain and actually speeds up the brain shrinkage that occurs with age.  This is associated with memory loss, symptoms of dementia and cognitive decline.

Physical exercise is touted as one of the key ways to protect against brain shrinkage and other age-related brain changes, and now it appears it may help protect against some of the brain damage caused by drinking.

Exercise May Help Protect Your Brain From Alcohol-Related Damage

Among 60 long-time drinkers, those who were the most physically active had less damaged white matter in their brains compared to those who were less active.1The white matter is considered the “wiring” of your brain’s communication system, and is known to decline in quality with age and heavy alcohol consumption.

Although the study didn’t prove a cause-and-effect relationship, the researchers concluded that “exercise may protect WM [white matter] integrity from alcohol-related damage,” continuing:2

“We cannot say whether exercise would necessarily improve white matter damage in individuals with a history of heavy drinking.

However, our findings in combination with the many well-established positive physiological and psychological benefits of aerobic exercise suggest that aerobic exercise could be potentially helpful for individuals with history of heavy alcohol use.”

Exercise Protects Your Brain From Shrinkage, Slows Cognitive Decline

One of the effects of chronic heavy drinking is that it speeds the shrinkage of key regions in your brain. Exercise is useful in this area, as research has shown that people who engaged in the most physical exercise showed the least amount of brain shrinkage, a protective effect that was even greater than that offered by mentally stimulating activities.3

Exercise encourages your brain to work at optimum capacity by causing nerve cells to multiply, strengthening their interconnections and protecting them from damage.

During exercise, nerve cells release proteins known as neurotrophic factors, such as brain-derived neurotrophic factor or BDNF, which activates brain stem cells to convert into new neurons. BDNF also triggers numerous other chemicals that promote neural health.

Scientific evidence shows that physical exercise helps you build a brain that not only resists shrinkage, but also increases cognitive abilities.4 In one review of more than 100 studies, both aerobic and resistance training were found to be important for maintaining cognitive and brain health in old age.5

Moderate exercise may even reverse normal brain shrinkage by 2 percent, effectively reversing age-related hippocampus degeneration, which is associated with dementia and poor memory, by one to two years.6 On the other hand, the people in the control group who didn’t exercise saw an average of 1.4 percentdecrease in hippocampus size.

Exercise is a Powerful Tool for Brain Health for Drinkers and Non-Drinkers Alike

The hippocampus region of your brain increases in size as a response to exercise, making this activity a powerful tool to fight the onset of Alzheimer’s disease. The hippocampus, which is considered the memory center of your brain, is the first region of your brain to suffer shrinkage and impairment at the onset of Alzheimer’s disease, leading to memory problems and disorientation.

Other contributing factors to brain disease caused by the normal aging process may also include a decrease in blood flow to your brain, and the accumulation of environmental toxins in your brain. Exercise can help ameliorate both of these conditions by increasing blood flow to your brain, thereby increasing oxygen supply to your brain and encouraging a more vigorous release and removal of accumulated toxins through better blood circulation.

If you’re a regular drinker, this becomes even more important, as alcohol is a neurotoxin that can poison your brain. Increased blood flow may also promote delivery of more of the nutrients necessary to keep your brain cells healthy in the first place.

Brain Exercises are Better than Drugs in Preventing Cognitive Decline

Exercise has been shown to be better than mentally stimulating activities like brain training exercises at protecting your brain, but mental “exercise” is still important. In fact, new research shows it works better than drugs in preventing cognitive decline. The analysis of 32 trials found that mental exercise, such as computer-based brain training programs or memory, reasoning and speed-processing exercises, protected against cognitive decline better than leading dementia drugs like donepezil. Research into brain plasticity has proven that your brain continues to make new neurons throughout life in response to mental activity, which means that cognitive function can be improved, regardless of your age, and cognitive decline can be reversed.

If you’re interested in mental exercises for your brain, Dr. Michael Merzenich, professor emeritus at the University of California, who has pioneered research in brain plasticity for more than 30 years, has been instrumental in the development of a kind of “brain gym” environment — a computer-based brain training program that can help you sharpen a range of skills, from reading and comprehension to improved memorization and more. The program is called Brain HQ.7

“There are some very useful exercises in there that are for free, and you can actually drive improvements, for example, in brain speed, in the accuracy, with which the brain represents information in detail,” he says. “Basically, what you’re doing is reducing the chatter, the noisiness of the process of your brain. That impacts your capacity, for example, to record that information, to remember it. Because when the information is in its degraded form, when it’s fuzzy, when it’s imprecise, all of the uses of it – like your brain makes basically – are degraded.”

In the above-mentioned study, those who used computer-based training programs had significantly better memory and attention skills, improvements that were, in some cases, retained even five years later.

Another Reason for Chronic Heavy Drinkers to Take Up Exercise

There’s little doubt that exercise is one of the most important aspects of optimal health – not only for your brain but also for your entire body. That said, if you or someone you love has been affected by alcohol abuse, you know the great toll it can take on your personal relationships, work life and ability to function normally on a day-to-day basis, let alone fit in regular workouts.

The cravings for alcohol can become all-consuming and eventually an alcoholic does not feel “normal” until they’ve had a drink. The alcohol abuse inevitably throws off your circadian rhythm — the normal times you eat, sleep and wake up — as well, leading to a downward spiral of health and emotional effects. When you drink, it forces your brain to release unnaturally elevated levels of dopamine, a chemical your brain associates with rewarding behaviors. When you exercise, however, this same reward chemical is released, which means you can get the same “buzz” from working out that you can get from a six-pack of beer, with far better outcomes for your health.

This is why, if you know you’re prone to alcohol abuse or have a family history of alcohol addiction, exercising regularly can greatly reduce your risk of becoming dependent.

For those already addicted, exercise is beneficial too, and may actually help to lessen cravings. Research has found, in fact, that hamsters that ran the most consumed less alcohol, while less active hamsters had greater cravings for and consumption of alcohol.8  By replacing drinking with exercise, you may find that the rewarding feeling you get from exercise provides you with a suitable alternative to the rewarding feeling you previously got from alcohol.

What Type of Fitness Program is Best?

Ideally, to truly optimize your health, you’ll want to strive for a varied and well-rounded fitness program that incorporates a variety of exercises. As a general rule, as soon as an exercise becomes easy to complete, you need to increase the intensity and/or try another exercise to keep challenging your body. I recommend incorporating the following types of exercise into your program:

  • High-Intensity Interval (Anaerobic) Training: This is when you alternate short bursts of high-intensity exercise with gentle recovery periods.
  • Strength Training: Rounding out your exercise program with a 1-set strength training routine will ensure that you’re really optimizing the possible health benefits of a regular exercise program. You need enough repetitions to exhaust your muscles. The weight should be heavy enough that this can be done in fewer than 12 repetitions, yet light enough to do a minimum of four repetitions. It is also important NOT to exercise the same muscle groups every day. They need at least two days of rest to recover, repair and rebuild.
  • You can also “up” the intensity by slowing it down. For more information about using super slow weight training as a form of high-intensity interval exercise, please see my interview with Dr. Doug McGuff.
  • Core Exercises: Your body has 29 core muscles located mostly in your back, abdomen and pelvis. This group of muscles provides the foundation for movement throughout your entire body, and strengthening them can help protect and support your back, make your spine and body less prone to injury and help you gain greater balance and stability. Exercise programs like Pilates and yoga are also great for strengthening your core muscles, as are specific exercises you can learn from a personal trainer.
  • Stretching: My favorite type of stretching is active isolated stretching developed by Aaron Mattes. With Active Isolated Stretching (AIS), you hold each stretch for only two seconds, which works with your body’s natural physiological makeup to improve circulation and increase the elasticity of muscle joints. This technique also allows your body to repair itself and prepare for daily activity. You can also use devices like the Power Plate to help you stretch.

Source: .mercola.com

Testosterone Surge after Exercise May Help Remodel the Mind .

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Most of the praise associated with exercise is typically geared toward its cardiovascular benefits and its role in weight loss and muscle toning/strength.

Often overlooked is the phenomenal role exercise plays in supporting your brain health and even spurring the creation of new brain cells (a process called neurogenesis).

Now researchers have revealed one of the mechanisms that makes exercise such a powerful tool for brain health: a natural boost in testosterone.

Exercise Boosts Brain Testosterone Levels, Builds New Brain Cells

The hippocampus is a major component of your brain. It belongs to the primitive part of your brain known as the limbic system and plays an important role in the consolidation of information from your short-term memory to long-term memory and spatial navigation. A new animal study found that not only does mild exercise activate hippocampal neurons, it actually promotes their growth. In the brain, this also, in turn, helps with the creation of new brain cells.1 Even though the study included only male rats, the scientists believe the results apply to humans.

Interestingly, researchers at Northwestern University‘s Feinberg School of Medicine in Chicago have discovered a couple of other mechanisms that help explain how exercise helps new brain cells to form.

It appears that exercise lowers the activity of bone-morphogenetic protein or BMP, which slows the production of new brain cells. At the same time, exercise increases Noggin, a brain protein that acts as a BMP antagonist. The more Noggin present in your brain, the less BMP activity there is, and the more stem cell divisions and neurogenesis (production of new brain cells) takes place.2

What’s the Best Type of Exercise for Boosting Testosterone?

Researchers from the featured study found that even mild to moderate exercise boosts testosterone enough to improve brain health. Short periods of intense exercise also have a proven positive effect on increasing testosterone levels and preventing its usual age-related decline (which typically begins around age 30 in men).

Additionally, combining short bursts of high-intensity exercise like Peak Fitness with intermittent fasting will also boost your growth hormone levels. Intermittent fasting boosts testosterone by increasing the expression of satiety hormones including insulin, leptin, adiponectin, glucagon-like peptide-1 (GLP-1), colecystokinin (CKK) and melanocortins, all of which are known to potentiate healthy testosterone actions, increase libido and prevent age-related testosterone decline.

You can find more information about this in an article previously written on intermittent fasting, and here’s a summary of what a typical high-intensity Peak Fitness routine might look like:

  • Warm up for three minutes
  • Exercise as hard and fast as you can for 30 seconds. You should feel like you couldn’t possibly go on another few seconds
  • Recover at a slow to moderate pace for 90 seconds
  • Repeat the high intensity exercise and recovery 7 more times

As you can see, the entire workout is only 20 minutes. That really is a beautiful thing. And within those 20 minutes, 75 percent of that time is warming up, recovering or cooling down. You’re really only working out intensely for four minutes. It’s hard to believe if you have never done this, that you can actually get that much benefit from only four minutes of intense exercise, but that’s all it is

If You Want a Healthy Brain, Exercise is a Must

Exercise boosts brain health through multiple pathways, many of them likely yet to be discovered. One study, for instance, revealed that when mice exercised, they grew an average of 6,000 new brain cells in every cubic millimeter of tissue sampled.3 The growth occurred in the hippocampus, which is considered the memory center of your brain, and the mice showed significant improvements in the ability to recall memories without any confusion.

Exactly why exercise has this effect isn’t entirely known, but researchers speculated it could be due to higher levels of hormones released, as discussed earlier, increased blood flow to your brain, or even stress reduction (the stress hormone cortisol may inhibit the growth of new brain cells).

Animal tests have illustrated that during exercise their nerve cells release proteins known as neurotrophic factors. One in particular, called brain-derived neurotrophic factor (BDNF), triggers numerous other chemicals that promote neural health, and has a direct benefit on cognitive functions, including enhanced learning. Further, exercise provides protective effects to your brain through:

  • The production of nerve-protecting compounds
  • Greater blood flow to your brain
  • Improved development and survival of neurons
  • Decreased risk of heart disease and stroke

So if you value your brainpower, you’ll want to make certain that exercise is a regular part of your life. Staying active with a variety of activities is best, as each type of exercise may offer unique benefits for your brain health and may even help your brain to grow as you get older, rather than shrink – which is the norm, sadly, as many people do not stay active as they age. Exercise is so powerful, yet it remains one of the most neglected areas of health. If you’re not already an avid exerciser, what’s holding you back?

Perhaps you believe your size is preventing you from exercising, or that it won’t make a big difference. Perhaps you have a handicap, or feel like you’re too old, too out of shape, or too frail to exercise.

Whatever your reason might be, try reading these examples of exercise inspiration. By the end, I suspect you may be ready to change your tune, and I hope, for your sake, that you are.

Exercising sets into motion a beneficial feedback loop that leads to greater levels of health body-wide, while lack of exercise makes your health spiral downward and opens the door to disease and premature aging. Health benefits of exercise expand far beyond even your muscles and your brain to include:

Improving your brainpower and boosting your IQ Lowering your risk of heart disease and cancer Building strong bones
Lowering your blood pressure Curing insomnia Losing weight
Relieving pain Balancing your mood and fighting depression Increasing your energy levels
Acquiring fewer colds Lowering your risk of diabetes and reversing pre-diabetes Slowing down your aging process
   

Source: Dr. Mercola

 

Want to Boost Your IQ? Get Better Grades? Work More Efficiently?

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Exercise isn’t just about losing weight or getting bigger biceps and six-pack abs.

More and more studies are showing that exercise can boost your intelligence and mental acuity, with brain benefits for grade-schoolers all the way up to working adults and seniors.

Exercise! In the infographic above, the evidence speaks loud and clear that regular exercise can improve test scores, IQ levels and task efficiency. Some of the research highlights include:1

  • Among elementary school students, 40 minutes of daily exercise increased IQ by an average of nearly 4 points
  • Among 6th graders, the fittest students scored 30 percent higher than average students, and the less fit students scored 20 percent lower
  • Among older students, those who play vigorous sports have a 20 percent improvement in Math, Science, English and Social Studies
  • Fit 18-year-olds are more likely to go on to higher education and get full-time jobs
  • Students who exercise before class improved test scores 17 percent, and those who worked out for 40 minutes improved an entire letter grade

Even once you’re in the workforce, exercise can be an invaluable tool to increase your performance and productivity. Research shows an employee who exercises regularly is 15 percent more efficient than those who do not, which means a fit employee only needs to work 42.5 hours in a week to do the same work as an average employee does in 50.2

Boosting Your Brain Power With Exercise

Most people don’t understand that your brain is pliable, and it can actually improve even after it is damaged. Exercise is a powerful way to encourage your brain to work at optimum capacity by causing nerve cells to multiply, strengthening their interconnections and protecting them from damage. Animal tests have illustrated that during exercise their nerve cells release proteins known as neurotrophic factors. One in particular, called brain-derived neurotrophic factor (BDNF), triggers numerous other chemicals that promote neural health, and has a direct benefit on cognitive functions, including enhanced learning.

Further, exercise provides protective effects to your brain through:

  • The production of nerve-protecting compounds
  • Greater blood flow to your brain
  • Improved development and survival of neurons
  • Decreased risk of cardiovascular diseases

So if you value your brainpower, you’ll want to make certain that exercise is a regular part of your life. Staying active with a variety of activities is best, as each type of exercise may offer unique benefits for your brain health and may even help your brain to grow as you get older, rather than shrink – which is the norm.

For instance, a review of more than 100 studies, published in the Journal of Applied Physiology, revealed that both aerobic and resistance training are important for maintaining cognitive and brain health in old age.3 Moderate exercise can reverse normal brain shrinkage by 2 percent, effectively reversing age-related hippocampus degeneration by one to two years.4 Also according to the study, the people in the control group who didn’t exercise saw an average of 1.4 percent decrease in hippocampus size.

Now listen up… when these researchers say the hippocampus region of the brain increases in size as a response to exercise, they are talking about a powerful tool to fight the onset of Alzheimer’s disease. The hippocampus, which is considered the memory center of your brain, is the first region of your brain to suffer shrinkage and impairment at the onset of Alzheimer’s disease, leading to memory problems and disorientation.

So not only can exercise boost your brain power from your childhood years on up, it can help keep your brain from shrinking once you’re older, so you can keep the brainpower you have.

Tips for a Well-Rounded Exercise Program

To get all the benefits exercise has to offer, you’ll want to strive for a varied and well-rounded fitness program that incorporates a variety of exercises. As a general rule, as soon as an exercise becomes easy to complete, you need to increase the intensity and/or try another exercise to keep challenging your body. I recommend incorporating the following types of exercise into your program:

  1. High-Intensity Interval (Anaerobic) Training: This is when you alternate short bursts of high-intensity exercise with gentle recovery periods. In the video below, you can see a demonstration of this in action using Peak Fitness.
  2. Strength Training: Rounding out your exercise program with a 1-set strength training routine will ensure that you’re really optimizing the possible health benefits of a regular exercise program. You can also “up” the intensity by slowing it down. For more information about using super slow weight training as a form of high-intensity interval exercise, please see my interview with Dr. Doug McGuff below.

Download Interview Transcript

  1. Core Exercises: Your body has 29 core muscles located mostly in your back, abdomen and pelvis. This group of muscles provides the foundation for movement throughout your entire body, and strengthening them can help protect and support your back, make your spine and body less prone to injury and help you gain greater balance and stability.

You need enough repetitions to exhaust your muscles. The weight should be heavy enough that this can be done in fewer than 12 repetitions, yet light enough to do a minimum of four repetitions. It is also important NOT to exercise the same muscle groups every day. They need at least two days of rest to recover, repair and rebuild. Exercise programs like Pilates and yoga are also great for strengthening your core muscles, as are specific exercises you can learn from a personal trainer.

  1. Stretching: My favorite type of stretching is active isolated stretches developed by Aaron Mattes. With Active Isolated Stretching, you hold each stretch for only two seconds, which works with your body’s natural physiological makeup to improve circulation and increase the elasticity of muscle joints. This technique also allows your body to repair itself and prepare for daily activity. You can also use devices like the Power Plate to help you stretch.

New Proof that Exercise Makes You Smarter

Wondering How to Get Your Kids Hooked on Exercise?

It’s easy to get kids “hooked” on video games and television, but getting them hooked on exercise is a gift that will last a lifetime.

Your child does not need to log 30-60 minutes in the gym or in a specific exercise class, unless that’s really what they want to do. A game of tag here, a bike ride there… short bursts of activity with periods of rest in between will work wonders, and kids will typically fall into this behavior quite spontaneously, as long as they’re outdoors and not cooped up in front of a TV or computer screen

Allow your child to choose activities that appeal to them and which are age appropriate. Remember that the trick to getting kids interested in exercise at a young age is to keep it fun. Gymnastics classes, sports, dance, hikes in the woods, canoeing, swimming, taking the dog for a walk… all count as “exercise” for kids (and for you!).

Of course, acting as a role model by staying active yourself is one of the best ways to motivate and inspire your kids. If your child sees you embracing exercise as a positive and important part of your lifestyle, they will naturally follow suit.

Source: mercola.com

Gut microflora and probiotics.

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There are 100 trillion cells in your body, but 90% of the genetic material is not yours. It is from the bacteria, fungi, viruses and other microorganisms, i.e. your microflora. Gut microbes are big in the news lately, as researchers continue to discover the important roles these tiny organisms play in your overall health and well-being. We now know that your microflora influence your:

  • Genetic expression
  • Immune system
  • Weight, and
  • Risk of numerous chronic and acute diseases, from diabetes to cancer

Most recently, research has shown that a certain set of these microbes may actually influence the activity of genes in your brain – and the parts they play are not small parts. They may work to manipulate your behavior, and your memory as well.

Microbes Manipulate Your Mind

According to a recent article in The Guardian1, certain species of gut bacteria have been found to influence gene activity in your brain. Some of this research was published in 2011.2 Mice lacking gut bacteria were found to engage in “high-risk behavior,” and this altered behavior was accompanied by neurochemical changes in the mouse brain.

According to the authors, microbiota (your gut flora) may play a role in the communication between your gut and your brain, and:

“Acquisition of intestinal microbiota in the immediate postnatal period has a defining impact on the development and function of the gastrointestinal, immune, neuroendocrine and metabolic systems. For example, the presence of gut microbiota regulates the set point for hypothalamic-pituitary-adrenal (HPA) axis activity.”

But they also discovered other differences between the mice with normal gut flora and those lacking gut bacteria. When examining the animals’ brains, they discovered a number of genetic alterations in the germ-free mice. According to The Guardian:

“Brain-derived neurotrophic factor (BDNF) was significantly up-regulated, and the 5HT1A serotonin receptor sub-type down-regulated, in the dentate gyrus of the hippocampus. The gene encoding the NR2B subunit of the NMDA receptor was also down-regulated in the amygdala.

All three genes have previously been implicated in emotion and anxiety-like behaviors.

BDNF is a growth factor that is essential for proper brain development, and a recent study showed that deleting the BDNF receptor TrkB alters the way in which newborn neurons integrate into hippocampal circuitry and increases anxiety-like behaviors in mice. Serotonin receptors, which are distributed widely throughout the brain, are well known to be involved in mood, and compounds that activate the 5HT1A subtype also produce anxiety-like behaviors.

The finding that the NR2B subunit of the NMDA receptor down-regulated in the amygdala is particularly interesting. NMDA receptors are composed of multiple subunits, but those made up of only NR2B subunits are known to be critical for the development and function of the amygdala, which has a well established role in fear and other emotions, and in learning and memory. Drugs that block these receptors have been shown to block the formation of fearful memories and to reduce the anxiety associated with alcohol withdrawal in rodents.”

Your Gut Bacteria Are Under Constant Assault

Your lifestyle can and does influence your gut flora on a daily basis. For example, your gut bacteria are extremely sensitive to:

All of these common exposures can wreak havoc on the makeup of bacteria in your gut, but researchers are now increasingly looking at the cascading ill effects of antibiotics in particular.

Not only are antibiotics overused in medicine, the vast majority of these drugs enter you via livestock – you consume antibiotics every time you eat meat from an animal raised in a confined animal feeding operation (CAFO). In fact, about 80 percent of all the antibiotics produced are used in agriculture3 – not only to fight infection, but to promote unhealthy (though profitable) weight gain in the animals.

Early Use of Antibiotics Also Linked to Obesity

With that in mind, is it any wonder that researchers are now finding that antibiotics are associated with weight gain in humans as well?

“For many years now, farmers have known that antibiotics are great at producing heavier cows for market,” Dr. Jan Blustein, MD, PhD, professor of population health and medicine told PreventDisease.com in a recent article.4 “While we need more research to confirm our findings, this carefully conducted study suggests that antibiotics influence weight gain in humans, and especially children…”

According to The Washington Post:5

“The use of antibiotics in young children might lead to a higher risk of obesity, and two new studies, one on mice and one on humans, conclude that changes of the intestinal bacteria caused by antibiotics could be responsible. Taken together, the New York University researchers conclude that it might be necessary to broaden our concept of the causes of obesity and urge more caution in using antibiotics.”

The first study, published in the journal Nature6, found that young mice treated with low doses of common antibiotics gained 10-15 percent more fat than the untreated controls. After surveying the gut bacteria in the mice, they found that mice treated with antibiotics had a different composition of gut bacteria compared to the untreated mice. Specifically, certain species of bacteria previously shown to be associated with obesity were found in higher concentrations in the treated mice. Furthermore, after genetic analysis of the bacteria’s metabolism, they discovered that genes responsible for fat synthesis had greater levels of activity in the treated mice.

According to lead author Martin Blaser:7

“The rise of obesity around the world is coincident with widespread antibiotic use, and our studies provide an experimental linkage. It is possible that early exposure to antibiotics primes children for obesity later in life.”

The co-author Dr Ilseung Cho added:8

“By using antibiotics, we found we can actually manipulate the population of bacteria and alter how they metabolize certain nutrients. Ultimately, we were able to affect body composition and development in young mice by changing their gut microbiome through this exposure.”

The second study, published in the International Journal of Obesity9, aimed to corroborate these findings in human subjects. The study, which included more than 10,000 children, found that treating babies with antibiotics before the age of six months old appears to predispose them to being overweight in childhood. Children exposed to antibiotics between the ages of six to 14 months did not have significantly higher body mass than unexposed children.

While this study does not prove causation between antibiotic use in infancy and later obesity, it does show a correlation, and the mechanism appears to be related to the way antibiotics alter your child’s gut flora. However, excess weight is not the only, or the worst problem that such imbalance can create. As previously explained by Dr. Natasha Campbell-McBride, children with imbalanced gut flora are more prone to develop neurological disorders, such as ADD/ADHD and various learning disorders. These children are also more prone to vaccine damage.

Prebiotics Research Highlighted at American Chemical Society Meeting

Increasingly, researchers are finding that proper nutrition is not just about getting the right kind and amount of nutrients needed for biological processes. You also need to nourish these non-human cells in your body, i.e. your gut microflora. This issue was recently raised at the 244th National Meeting & Exposition of the American Chemical Society. According to a recent article in NewHope360:10

“‘Just as people need food to thrive, so do the billions of healthful bacteria that live in our guts, our gastrointestinal tract,’ [Robert] Rastall [Phd] explained. ‘There’s a large and expanding body of scientific evidence that bacteria in the gut play a role in health and disease. Prebiotics are foods that contain nutrients that support the growth and activity of these friendly bacteria.’

Rastall contrasted prebiotics to the more familiar probiotics, already being promoted on the labels of food like yogurt and some dietary supplements.

Probiotic foods actually contain friendly bacteria like Lactobacillus acidophilus believed to release healthful substances as they grow in the GI tract. Prebiotics are indigestible food ingredients that provide no nutrition to people. Their purpose is to nourish the friendly bacteria among the estimated 100 trillion microbes living inside the human GI tract.”

While raised awareness about the importance of prebiotics and probiotics is good news, it comes with the territory that researchers are also working on ways to produce prebiotics that can easily be added to processed foods. Pre- and probiotics are very sensitive to heat, and excessive heat-treatment is a hallmark of most processed foods. It therefore stands to reason that any prebiotic inventions they come up with for the processed foods market will inevitably be of inferior quality, and I strongly recommend avoiding any and all processed foods that proclaim to contain prebiotics or probiotics, and stick with the real thing, i.e. traditionally fermented foods for healthful probiotics, and unprocessed whole foods for prebiotics, such as onions and garlic.

Study Finds “Clear Link” Between Inflammation, Bacterial Communities and Cancer

Demonstrating just how far-reaching the health impact of the bacterial balance in your gut can be, another recent study claims the key factor behind cancer appears to be ecological rather than genetic.11

Published in the journal Science12, the study suggests cancer may be due to a chain reaction that starts with inflammation that disrupts your gut ecosystems, allowing pathogens, such as E.coli, to invade your gut and cause cellular damage. The presence of E.coli was increased by a factor of 100 by inflammation, and 80 percent of germ-free mice infected with E.coli developed colorectal cancer, while germ-free mice inoculated with another common gut bacterium remained cancer-free, although these mice, like the others, did develop severe colitis (gut inflammation).

According to a press release by the University of North Carolina:13

“In a series of experiments conducted with mice prone to intestinal inflammation, the researchers found that inflammation itself causes significant simplification in diverse communities of gut microbes and allows new bacterial populations to establish major footholds. Among the bacterial taxa invading the disturbed intestinal ecosystem, the research team found a greatly increased presence of E. coli and related bacteria.

By putting E. coli bacteria into mice that were raised under sterile conditions, the team also found that the presence of E. coli promoted tumor formation. When regions of the E. coli genome known to be involved in DNA damage were removed, the ability of the E. coli to cause tumors was substantially decreased.

The researchers noted that the mouse results may have implications for human health as well, as they also found an E. coli variant with the suspect genes in high percentages of human patients with colorectal cancer and irritable bowel disease.

…’As is usual in human studies, we didn’t have cause and effect,’ Fodor noted. ‘We don’t know if microbes are somehow causing conditions to shift in the gut that would cause cancer or if there are conditions that are associated with cancer that would increase the openness of the gut to particular microbes. A shift in the microbial community is associated with inflammation… It is interesting that the microbial community is actually changing with the disease state, which indicates that it is either responding to or contributing to the disease state.'”

Like Bacteria, Cancer Cells Rely on Communication and Cooperation

In related news, an article published in Trends in Microbiology14 examines the shared traits of cancer cells and bacteria. Bacteria and cancer cells both use sophisticated communication to gain supremacy within the host. As reported by Medical News Today:15

“Inspired by the social and survival tactics of bacteria, the team presents a new picture of cancer as a meta-community of smart communicating cells possessing special traits for cooperative behavior. Using intricate communication, cancer cells can distribute tasks, share resources, differentiate, and make decisions. Before sending cells to colonize organs and tissues throughout the body (metastasis), ‘spying cells’ explore the body and return the cancer’s origin. Only then do metastatic cells leave the primary tumor and navigate to new posts.

Also like bacteria, cancer cells change their own environment. They induce genetic changes and enslave surrounding normal cells, forcing them to do the disease’s bidding – providing physical support, protecting them from the immune system, and more.”

Three years ago, I posted a TED video featuring Bonnie Bassler, in which she discusses how bacteria “talk” to each other using a chemical language that lets them coordinate defense and mount attacks. Cancer cells, as it turns out, employ similar forms of communication, and as discussed by Bassler, these discoveries pave the way for the development of drugs aimed at shutting down or altering cell-to-cell communication.

According to Medical News Today:

“The team also suggests further research into cancer ‘cannibalism,’ when cancer cells may consume their peers when they run out of resources. The idea is to send signals which trigger cancer cells to kill each other, which can be done with bacteria. Other researchers have demonstrated that injected bacteria can ‘outsmart cancer.’ Bacteria can be used to induce gap junctions between the cancer cells and immune cells, ‘teaching’ the immune system to recognize and kill the tumor cells.”

The Phenomenal Health Benefits of Fermented Vegetables

Cultured or fermented foods have a very long history in virtually all native diets, and have always been highly prized for their health benefits. The advent of processed foods dramatically altered the human diet, and we’re now reaping the results in the form of rapidly rising chronic health problems. I believe the shunning of traditionally fermented foods has a lot to do with this.

The culturing process produces beneficial microbes that are extremely important for your health as they help balance your intestinal flora. If you do not regularly consume the traditionally fermented foods below, a high-quality probiotic supplement will provide similar benefits:

  • Fermented vegetables
  • Lassi (an Indian yoghurt drink, traditionally enjoyed before dinner)
  • Fermented milk, such as kefir (a quart of unpasteurized kefir has far more active bacteria than you can possibly purchase in any probiotics supplement)
  • Natto (fermented soy)

When choosing fermented foods, steer clear of pasteurized versions, as pasteurization will destroy many of the naturally occurring probiotics. This includes most of the “probiotic” yogurts you find in every grocery store these days; since they’re pasteurized, they will be associated with all of the problems of pasteurized milk products and they typically contain added sugars, high fructose corn syrup, artificial coloring, or artificial sweeteners, all of which will only worsen your health.

Fermented foods are also some of the best chelators and detox agents available, meaning they can help rid your body of a wide variety of toxins, including heavy metals.

When you first start out, you’ll want to start small, adding as little as half a tablespoon of fermented vegetables to each meal, and gradually working your way up to about a quarter to half a cup (2 oz to 4 oz) of fermented vegetables or other cultured food with one to three meals per day. Since cultured foods are efficient detoxifiers, you may experience detox symptoms, or a “healing crisis,” if you introduce too many at once.

Learn to Make Your Own Fermented Vegetables

Fermented vegetables are easy to make on your own. It’s also the most cost-effective way to get high amounts of healthful probiotics in your diet. To learn how, review the following interview with Caroline Barringer, a Nutritional Therapy Practitioner (NTP) and an expert in the preparation of the foods prescribed in Dr. Natasha Campbell-McBride’s Gut and Psychology Syndrome (GAPS) Nutritional Program. In addition to the wealth of information shared in this interview, I highly recommend getting the book Gut and Psychology Syndrome, which provides all the necessary details for Dr. McBride’s GAPS protocol.

Although you can use the native bacteria on cabbage and other vegetables, it is typically easier to get consistent results by using a starter culture. Caroline prepares hundreds of quarts of fermented vegetables a week and has found that she gets great results by using three to four high quality probiotic capsules to jump start the fermentation process.

Caroline prepares the vegetables commercially and I used hers for a month before I started making my own. So, if you just want to put your toe in the water and see if you like them, you can order a jar or two and try them out. You can find her products on www.CulturedVegetables.net or www.CulturedNutrition.com.

AVOID This to Optimize Your Gut Flora!

Along with eating naturally fermented foods and/or taking a high-quality supplement, it’s essential that you avoid sugar, including fructose. Sugar nourishes pathogenic bacteria, yeast, and fungi in your gut, which may actually harm you more than its impact on insulin resistance. One of the major results of eating a healthy diet like the one described in my nutrition plan is that you cause your beneficial gut bacteria to flourish, and they secondarily perform the real “magic” of restoring your health.

Remember, an estimated 80 percent of your immune system is located in your gut, which is just one more reason why “tending to” your gut microflora is an essential element of good health. A robust immune system, supported by your flourishing inner ecosystem, is your number one defense against ALL disease, from the common cold to cancer.

I feel very strongly that if we can catalyze a movement to get more people to implement this ancient dietary wisdom to their normal eating patterns, then we’ll start seeing a radical change in health.

Sources and References

Source: Dr. Mercola

How Serotonin Reuptake Inhibitors Work: Understanding More Fundamental Mechanisms of Action.

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By stimulating microRNA miR-16 in the midline serotonergic raphe, fluoxetine initiates signaling cascades that lead to hippocampal neurogenesis.

Several lines of evidence suggest that in adults, antidepressant therapies enhance neurogenesis in the hippocampus, but how this process occurs has been unclear. These researchers studied the effects of fluoxetine in mice and in humans. They worked out several pathways that begin with the stimulation by fluoxetine of the microRNA miR-16 in serotonergic neurons in raphe and ultimately result in hippocampal neurogenesis.

In a series of experiments in mice, fluoxetine activated raphe miR-16, which decreased raphe levels of the serotonin reuptake transporter (SERT). In turn, these events directly caused brain-derived neurotropic factor (BDNF) and two other signaling molecules to act on the hippocampus. Indirectly, the same events resulted in release of another protein from the raphe nuclei, S100β, which in turn stimulated the locus coeruleus to induce SERT and secrete serotonin. Both the direct and indirect pathways caused decreases in hippocampal miR-16, which sequentially led to increases in both hippocampal SERT and the bcl-2 protein (which promotes neurotrophic function), which in turn stimulated neurogenesis. In nine patients with major depression, 12-week fluoxetine treatment increased levels of the three signaling molecules in cerebrospinal fluid. The interventions were accompanied by improvements in several mouse models of depression, as well as in the patients. See accompanying figure.

Comment: These findings draw together several seemingly unconnected lines of research. The authors identify miR-16 as a “missing link” between serotonin reuptake inhibitor treatment and hippocampal neurogenesis and as a “micromanager” of the intervening changes in the raphe nucleus, locus coeruleus, serotonin receptor transporter, serotonin secretion, and hippocampal neurogenesis. The processes appear to work through the cooperative and integrated activities of several signaling molecules. Further clarification of these pathways may help refine therapeutic strategies for depressive disorders.

Source: Journal Watch Psychiatry