Promising Therapeutic Target Uncovered to Treat Stress-Related Sleep Disorders


New research from the Perelman School of Medicine at the University of Pennsylvania reveals neurons in the preoptic hypothalamus—the region of the brain that regulates sleep and body temperature—are rhythmically activated during non-rapid eye movement sleep (NREM). Stress activates these brain cells out of turn, causing “microarousals,” that interrupt sleep cycles and decrease the duration of sleep episodes.

young beautiful hispanic woman at home bedroom lying in bed late at night trying to sleep suffering insomnia sleeping disorder or scared on nightmares looking sad worried and stressed

The findings are published in Current Biology in an article titled, “Regulation of stress-induced sleep fragmentation by preoptic glutamatergic neurons.”

“When you have a bad night of sleep, you notice that your memory isn’t as good as it normally is, or your emotions are all over the place—but a bad night of sleep interrupts so many other processes throughout your body. This is even more heightened in individuals with stress-related sleep disorders,” said senior author, Shinjae Chung, PhD, an assistant professor of neuroscience. “It’s crucial to understand the biology driving the brain activity in these crucial stages of sleep, and how stimuli like stress can disrupt it, so that we might someday develop therapies to help individuals have more restful sleep that allows their brain to complete these important processes.”

The researchers monitored the activity in the preoptic area (POA) of the hypothalamus of mice during their natural sleep and found that glutamatergic neurons (VGLUT2) are rhythmically activated during NREM sleep. They also found that VGLUT2 neurons were most active during wakefulness, and less active during NREM and REM sleep.

During microarousals in NREM sleep, VGLUT2 neurons were the only active neurons within the POA, and their signals started to increase in the time before a microarousal. To confirm that active VGLUT2 neurons were indeed the cause of microarousal, the researchers stimulated the VGLUT2 neurons in sleeping subjects, which immediately increased the amount of microarousals and wakefulness.

To illustrate the connection between stress and increased VGLUT2 neuron activation, researchers exposed subjects to a stressor, which increased awake time and microarousals, and decreased overall time spent in REM and NREM sleep. Researchers also noted increased VGLUT2 neuron activity during NREM sleep in the stressed subjects. What’s more, when researchers inhibited VGLUT 2 neurons, microarousals during NREM sleep decreased, and NREM sleep episodes were longer.

“The glutamatergic neurons in the hypothalamus give us a promising target for developing treatments for stress-related sleep disorders,” said first author, Jennifer Smith, a graduate researcher in Chung’s lab. “Being able to reduce interruptions during the important stages of non-REM sleep by suppressing VGLUT2 activity would be groundbreaking for individuals struggling with disrupted sleep from disorders like insomnia or PTSD.”

Can Prebiotic Foods Improve Your Sleep?


prebiotic foods improve sleep

Story at-a-glance

  • Research demonstrates the bacteria in your gut are integral to your health and well-being, and may influence your genes and your immune system
  • Recent research now links prebiotic foods, which nourish beneficial bacteria, with improved sleep patterns and better repair of stress damage during sleep
  • Stress impacts sleep quality, which in turn increases your risk for health problems, accidents, and reduces cognitive performance; tips to improve sleep include prebiotics, reducing light, temperature control and more

The bacteria living in your gut do more than help your body digest and metabolize the food you eat. A myriad of research studies demonstrate these bacteria are integral to your health and well-being, and may positively influence the activity of hundreds of your genes and your immune system.

When you add friendly bacteria to your intestinal tract they are called probiotics. Another way of impacting the friendly bacteria in your gut is to provide them with the nutrients they need to multiply. These nutrients are called prebiotics.

Prebiotics are found primarily in fiber-rich foods. Friendly bacteria thrive on indigestible fiber. Inulin is one type of water-soluble fiber found in onions, garlic, leeks and asparagus that help nourish the beneficial bacteria in your gut.

Now researchers have found dietary prebiotics have a significant effect on rapid-eye-movement (REM) and non-rapid-eye-movement (NREM) sleep cycles, which may positively affect your sleep quality.1

Prebiotics Study

Researchers studied the effect of prebiotics on gut health and REM sleep of young rats. The test animals were given a diet rich in prebiotics starting when they were 3 weeks old.2

The researchers noted that in previous studies, results suggested daily stress could alter your gut microbiome in a way that would alter your sleep-wake cycle. Their goal was to determine if using prebiotics might help improve sleep quality under stress.

The rats were fed a manufactured diet containing prebiotic fiber or a control diet for four weeks. After the first four weeks the researchers analyzed the excrement and found those eating prebiotics had an increase in beneficial gut bacteria, compared to the control group.3

As the friendly bacteria metabolize the prebiotic fiber, they not only grow and multiply but also excrete a metabolite beneficial to your brain health.4 Rats eating the diet rich in prebiotics also spent more time in restful and restorative NREM sleep than those eating the control diet. The researchers wrote:5

“Given that sufficient NREM sleep and proper nutrition can impact brain development and function and that sleep problems are common in early life, it is possible that a diet rich in prebiotics started in early life could help improve sleep, support the gut microbiota and promote optimal brain/psychological health.”

The test group also benefited when stressed. Researchers found they spent more time in REM sleep after being stressed, which is important for promoting recovery.6Prior research has found people who get more REM sleep after a significant trauma are less likely to suffer post-traumatic stress disorder.7

Prebiotics May Improve a Depleted Gut

While fiber is an excellent prebiotic for friendly bacteria, sugar and carbohydrates are the nutrients your unfriendly bacteria use to grow and multiply. If you eat a typical Western diet, high in processed foods and refined carbohydrates, your gut microbiome may not have enough beneficial bacteria to keep you healthy.

The test group of rats in the study did not experience a stress disruption of their gut microbiome, as did the control group of rats, and returned to normal sleep patterns more quickly than the control group as well.8

The results of this study only contribute to current research demonstrating the importance of gut health on inflammation, obesity, depression, metabolic syndrome and insulin resistance.

Although all prebiotics are fiber, not all fiber has a prebiotic effect on friendly bacteria.9 To be classified as a prebiotic the fiber must resist gastric acidity, resist absorption in the upper gastrointestinal tract, be fermented by intestinal flora, and stimulate the growth or activity of beneficial bacteria.

The role of fiber in the diet has also been associated with improved bowel movements and reducing risk factors with cardiovascular disease, weight management, digestive health and immune function.

Increasing your intake of foods rich in prebiotic fiber may help improve your gut health, your sleep-wake cycles and reduce your risk for health conditions affected by lack of fiber.

Get Prebiotics Daily

As the benefits of prebiotics are becoming better known, food manufacturers are climbing on the bandwagon, advertising the benefits of fiber in their products.

However, as with most dietary choices, the best prebiotic fiber is found in raw, whole foods, since most manufactured foods also contain some form of sugar, which feeds your unfriendly bacteria.

It is not always possible to eat enough foods rich in prebiotic fiber to nourish your beneficial bacteria. If you’re looking for a healthy way to supplement your fiber intake, organic whole husk psyllium is a simple, cost-effective way to do it.

Taking it three times a day could add as much as 18 grams of dietary fiber (soluble and insoluble) to your diet, which brings you quite close to the recommended minimum of 50 grams per 1,000 calories consumed when added to a healthy, veggie-rich diet.

Please keep in mind that psyllium is a heavily sprayed crop, which means many sources are contaminated with pesticides, herbicides and fertilizers. For this reason, be sure to use only organic psyllium husk, and ensure it’s 100 percent pure.

Many supplement brands use synthetic or semi-synthetic active ingredients that do not contain psyllium, such as methylcellulose and calcium polycarbophil. The following whole foods help add prebiotic fiber to your diet and improve the health of your microbiome, thus improving your overall health.10,11,12

Onions Leeks Garlic
Chicory root Banana Apples
Konjac root Burdock root Jicama
Seaweed Jerusalem artichokes Shallots
Asparagus Beetroot Fennel bulb
Green peas Snow peas Savoy cabbage
Chickpeas Lentils Red kidney beans
Nectarines Persimmon Tamarillo
Grapefruit Pomegranate Couscous
Cashews Pistachio nuts Breast milk

Dangers of Stress

Stress not only can negatively impact your sleep quality, but has been implicated in the development of other health conditions such as anxiety, heart disease and stroke.

Renowned author and award-winning neurobiologist Robert Sapolsky, Ph.D., speaks about this in the documentary, “Stress: Portrait of a Killer,” which was jointly produced by National Geographic and Stanford University, where Sapolsky is a professor.

In the film, Sapolsky warns us that13 “Stress is not a state of mind … it’s measurable and dangerous, and humans can’t seem to find their off-switch.” Your stress response saves lives when it enables you to run from predators or rescue someone from a burning building.

But, this same “life-saving” reaction becomes chronic when you need to cope with the rising cost of fuel, fear of public speaking or managing a difficult work situation. The documentary demonstrates how stress may shrink your brain, add fat to your belly and even shorten your life.

Stress also has a significant impact on the quality of your sleep, which in turn has an impact on your ability to cope with stress. It’s a vicious cycle that may increase your risk of suffering negative health conditions.

Importance of Quality Sleep

You’ve probably experienced working through a day after a poor night of sleep. You feel groggy, you may not have been able to think as clearly and you likely spent the day yawning. Lack of sleep has a significant impact on your cognitive functioning,14 and driving on five hours of sleep or less is like driving drunk to your brain.15

Quality sleep is not only important to your immediate health, mood, energy and daily functioning, but a chronic lack of sleep has a significant impact on your long-term health as well. Chronic loss of sleep puts you at risk for:16

Heart disease Heart failure Diabetes
Irregular heart rate High blood pressure Stroke
Loss of sex drive Depression Obesity
Impaired judgment Increased risk of dementia17 Increased risk of accidents or injury

Tips for Quality Sleep

Eating enough foods rich in prebiotic fiber or taking an additional supplement is one way to help improve the quality of your sleep. Here are several more tips, that when combined, may help you enjoy a quality eight or nine hours of sleep each night and effectively reduce your potential risk for illnesses associated with chronic sleep deprivation. For more tips to a restful night of sleep see my previous article, “16 Chronological Tips to Improve Your Sleep.”

Enjoy Exposure to Bright Sunlight Every Morning

Exposure to bright light first thing in the morning stops production of the sleep-inducing hormone melatonin and signals to your body that it’s time to wake up. Outdoor sunlight is best, so you might even want to take a quick walk outside.

Daily Exercise

Exercise leads to better sleep at night. Many people schedule their full workouts for morning, which makes it easier to also exercise while fasting (an added benefit). If you don’t have time for a full workout, at least do some quick stretching or bodyweight exercises.

Daily Walk Outside After Lunch

Not only will this increase in physical activity help you sleep later, but taking your walk outdoors gives you more exposure to bright sunlight. Light intensity is measured in lux units, and on any given day, the outdoor lux units will be around 100,000 at noon.

Indoors, the typical average is somewhere between 100 to 2,000 lux units — about two orders of magnitude less. The brightness of the light matters, because your pineal gland produces melatonin roughly in approximation to the contrast of bright sun exposure in the day and complete darkness at night.

If you are in relative darkness all day long, it can’t appreciate the difference and will not optimize your melatonin production. This, in turn, can have some rather significant ramifications for your health and sleep.

I take a one-hour walk every day in the bright sunlight on the beach, so along with boosting my vitamin D, I also anchor my circadian rhythm at the same time and I rarely ever have trouble sleeping.

Cut the Caffeine in Early Afternoon

If you’re a coffee drinker, take your last caffeinated sip in the early afternoon (this applies to caffeinated soda, too). The caffeine can linger in your body for hours, blocking a brain chemical called adenosine that would otherwise help you to fall asleep.

Light Dinner and No Food Three Hours Before Bed

If you eat a heavy meal too close to bedtime, your body will have to devote energy to digesting your food when it should be recharging during sleep. As part of Peak Fasting, I also recommend that you stop eating three hours before bed and don’t have your first meal until 13 to 18 hours later.

Take 15 Minutes to Unwind

If you’re stressed, it’s harder to fall asleep and stay asleep. Taking 15 minutes (at least) at the end of each day to relax may help your sleep significantly. You may try listening to music, journaling, meditation, chatting with a neighbor or the Emotional Freedom Techniques (EFT). Do whatever works best for you.

Avoid Blue Light at Night

In the evening (around 8 p.m.), you’ll want to dim your lights and turn off electronic devices. Normally, your brain starts secreting melatonin between 9 p.m. and 10 p.m., and these devices emit light that may stifle that process. After sundown, shift to a low-wattage bulb with yellow, orange or red light if you need illumination.

A salt lamp illuminated by a 5-watt bulb is an ideal solution that will not interfere with your melatonin production. If using a computer or smartphone, install blue light-blocking software like Iris, which is an improvement over f.lux. The program automatically alters the color temperature of your screen as the day goes on, pulling out the blue wavelengths as it gets late.

The easiest solution, however, is to simply use amber-colored glasses that block blue light. I found an Uvex model (S1933X) on Amazon that costs less than $10 and works like a charm to eliminate virtually all blue light.

This way you don’t have to worry about installing programs on all your devices or buying special light bulbs for evening use. Once you have your glasses on, it doesn’t matter what light sources you have on in your house.

Reduce Noise, Temperature and Light

Noise louder than a normal conversation may stimulate your nervous system and keep you awake. You may want to use a fan or other form of white noise to drown out noise disturbances while you sleep.

Thermoregulation — your body’s heat distribution system — is strongly linked to sleep cycles. When you sleep, your body’s internal temperature drops to its lowest level, generally about four hours after you fall asleep. Scientists believe a cooler bedroom may therefore be most conducive to sleep, since it mimics your body’s natural temperature drop.

Once you’re ready to climb into bed, make sure your bedroom is pitch black. The slightest bit of light in your bedroom can disrupt your body’s clock and your pineal gland’s melatonin production. You may want to cover your windows with drapes or blackout shades to achieve this and, if this isn’t possible, wear an eye mask.

Dos and Don’ts to Optimizing Your Gut Microbiome

Feeding your beneficial bacteria with prebiotics is more effective when you have a variety of friendly bacteria growing in your intestinal tract. Optimizing your gut microbiome may be one of the most important things you can do for your health. It is critical for a well-functioning immune system, and to help you normalize your sleep-wake cycles.

However, while vital, it is not very complicated. You will need to take proactive steps to implement certain key strategies and actively avoid other factors. To optimize your gut microbiome, consider the following recommendations:

Do: Avoid:
Eat plenty of fermented foods. Healthy choices include lassi, fermented grass-fed organic milk such as kefir, natto (fermented soy) and fermented vegetables.

If you ferment your own, consider using a special starter culture that has been optimized with bacterial strains that produce high levels of vitamin K2.

This is an inexpensive way to optimize your K2, which is particularly important if you’re taking a vitamin D3 supplement.

Antibiotics, unless absolutely necessary (and when you do, make sure to reseed your gut with fermented foods and/or a probiotic supplement).

While researchers are looking into methods that might ameliorate the destruction of beneficial bacteria by antibiotics,18,19 your best bet is likely always going to be reseeding your gut with probiotics from fermented and cultured foods and/or a high-quality probiotic supplement.

Take a probiotic supplement. Although I’m not a major proponent of taking many supplements (as I believe the majority of your nutrients need to come from food), probiotics are an exception if you don’t eat fermented foods on a regular basis Conventionally-raised, non-grassfed meats and other animal products, as CAFO animals are routinely fed low-dose antibiotics, plus genetically engineered grains loaded with glyphosate, which is widely known to kill many bacteria.
Boost your soluble and insoluble fiber intake, focusing on vegetables, nuts and seeds, including sprouted seeds. Chlorinated and/or fluoridated water.
Get your hands dirty in the garden. Germ-free living may not be in your best interest, as the loss of healthy bacteria can have wide-ranging influence on your mental, emotional and physical health.

Exposure to bacteria and viruses can help strengthen your immune system naturally, providing long-lasting immunity against disease.

Getting your hands dirty in the garden can help reacquaint your immune system with beneficial microorganisms on the plants and in the soil.

According to a recent report,20 lack of exposure to the outdoors can in and of itself cause your microbiome to become “deficient.”

Processed foods. Excessive sugars, along with otherwise “dead” nutrients, feed pathogenic bacteria.

Food emulsifiers such as polysorbate 80, lecithin, carrageenan, polyglycerols and xanthan gum also appear to have an adverse effect on your gut flora.21

Unless 100 percent organic, they may also contain genetically engineered ingredients that tend to be heavily contaminated with pesticides such as glyphosate.

Artificial sweeteners have also been found to alter gut bacteria in adverse ways.22

Open your windows. For the vast majority of human history the outside was always part of the inside, and at no moment during our day were we ever really separated from nature.

Today, we spend 90 percent of our lives indoors. And, although keeping the outside out does have its advantages it has also changed the microbiome of your home.

Research23 shows that opening a window and increasing natural airflow can improve the diversity and health of the microbes in your home, which in turn benefit you.

Agricultural chemicals, glyphosate (Roundup) in particular is a known antibiotic and will actively kill many of your beneficial gut microbes if you eat and foods contaminated with Roundup.
Wash your dishes by hand instead of in the dishwasher. Research has shown that washing your dishes by hand leaves more bacteria on the dishes than dishwashers do, and that eating off these less-than-sterile dishes may actually decrease your risk of allergies by stimulating your immune system. Antibacterial soaps, as they too kill off both good and bad bacteria, and contribute to the development of antibiotic-resistance.

Idiopathic REM sleep behaviour disorder in the development of Parkinson’s disease.


Parkinson’s disease is a progressive neurodegenerative disorder associated with Lewy body disease pathology in central and peripheral nervous system structures. Although the cause of Parkinson’s disease is not fully understood, clinicopathological analyses have led to the development of a staging system for Lewy body disease-associated pathological changes. This system posits a predictable topography of progression of Lewy body disease in the CNS, beginning in olfactory structures and the medulla, then progressing rostrally from the medulla to the pons, then to midbrain and substantia nigra, limbic structures, and neocortical structures. If this topography and temporal evolution of Lewy body disease does occur, other manifestations of the disease as a result of degeneration of olfactory and pontomedullary structures could theoretically begin many years before the development of prominent nigral degeneration and the associated parkinsonian features of Parkinson’s disease. One such manifestation of prodromal Parkinson’s disease is rapid eye movement (REM) sleep behaviour disorder, which is a parasomnia manifested by vivid dreams associated with dream enactment behaviour during REM sleep. Findings from animal and human studies have suggested that lesions or dysfunction in REM sleep and motor control circuitry in the pontomedullary structures cause REM sleep behaviour disorder phenomenology, and degeneration of these structures might explain the presence of REM sleep behaviour disorder years or decades before the onset of parkinsonism in people who develop Parkinson’s disease.

Source: Lancet