Summary: Researchers report a significant decrease in cerebral blood flow after physically fit older adults stop exercising for a short period of time.

Source: University of Maryland.

We all know that we can quickly lose cardiovascular endurance if we stop exercising for a few weeks, but what impact does the cessation of exercise have on our brains? New research led by University of Maryland School of Public Health researchers examined cerebral blood flow in healthy, physically fit older adults (ages 50-80 years) before and after a 10-day period during which they stopped all exercise. Using MRI brain imaging techniques, they found a significant decrease in blood flow to several brain regions, including the hippocampus, after they stopped their exercise routines.

“We know that the hippocampus plays an important role in learning and memory and is one of the first brain regions to shrink in people with Alzheimer’s disease,” says Dr. J. Carson Smith, associate professor of kinesiology and lead author of the study, which is published in Frontiers in Aging Neuroscience in August 2016. “In rodents, the hippocampus responds to exercise training by increasing the growth of new blood vessels and new neurons, and in older people, exercise can help protect the hippocampus from shrinking. So, it is significant that people who stopped exercising for only 10 days showed a decrease in brain blood flow in brain regions that are important for maintaining brain health.”

The study participants were all “master athletes,” defined as people between the ages of 50 and 80 (average age was 61) who have at least 15 years history of participating in endurance exercise and who have recently competed in an endurance event. Their exercise regimens must have entailed at least four hours of high intensity endurance training each week. On average, they were running ~36 miles (59 km) each week or the equivalent of a 10K run a day! Not surprisingly, this group had a V02 max above 90% for their age. This is a measure of the maximal rate of oxygen consumption of an individual and reflects their aerobic physical fitness.

Dr. Smith and colleagues measured the velocity of blood flow in brain with an MRI scan while they were still following their regular training routine (at peak fitness) and again after 10 days of no exercise. They found that resting cerebral blood flow significantly decreased in eight brain regions, including the areas of the left and right hippocampus and several regions known to be part of the brain’s “default mode network” – a neural network known to deteriorate quickly with a diagnosis of Alzheimer’s disease. This information adds to the growing scientific understanding of the impact of physical activity on cognitive health.

“We know that if you are less physically active, you are more likely to have cognitive problems and dementia as you age,” says Dr. Smith. “However, we did not find any evidence that cognitive abilities worsened after stopping exercising for just 10 days. But the take home message is simple – if you do stop exercising for 10 days, just as you will quickly lose your cardiovascular fitness, you will also experience a decrease in blood brain flow.”

Dr. Smith believes that this could have important implications for brain health in older adults, and points to the need for more research to understand how fast these changes occur, what the long term effects could be, and how fast they could be reversed when exercise is resumed.

Funding: This study was supported by a grant from the National Institutes of Health (HL098810). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Source: Kelly Blake – University of Maryland
Image Source: This NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “Hippocampal and Cerebral Blood Flow after Exercise Cessation in Master Athletes” by Alfonso J. Alfini, Lauren R. Weiss, Brooks P. Leitner, Theresa J. Smith, James M. Hagberg and J. Carson Smith in Frontiers in Aging Neuroscience. Published online August 5 2016 doi:10.3389/fnagi.2016.00184

Abstract

Hippocampal and Cerebral Blood Flow after Exercise Cessation in Master Athletes

While endurance exercise training improves cerebrovascular health and has neurotrophic effects within the hippocampus, the effects of stopping this exercise on the brain remain unclear. Our aim was to measure the effects of 10 days of detraining on resting cerebral blood flow (rCBF) in gray matter and the hippocampus in healthy and physically fit older adults. We hypothesized that rCBF would decrease in the hippocampus after a 10-day cessation of exercise training. Twelve master athletes, defined as older adults (age ≥ 50 years) with long-term endurance training histories (≥15 years), were recruited from local running clubs. After screening, eligible participants were asked to cease all training and vigorous physical activity for 10 consecutive days. Before and immediately after the exercise cessation period, rCBF was measured with perfusion-weighted MRI. A voxel-wise analysis was used in gray matter, and the hippocampus was selected a priori as a structurally defined region of interest (ROI), to detect rCBF changes over time. Resting CBF significantly decreased in eight gray matter brain regions. These regions included: (L) inferior temporal gyrus, fusiform gyrus, inferior parietal lobule, (R) cerebellar tonsil, lingual gyrus, precuneus, and bilateral cerebellum (FWE p < 0.05). Additionally, rCBF within the left and right hippocampus significantly decreased after 10 days of no exercise training. These findings suggest that the cerebrovascular system, including the regulation of resting hippocampal blood flow, is responsive to short-term decreases in exercise training among master athletes. Cessation of exercise training among physically fit individuals may provide a novel method to assess the effects of acute exercise and exercise training on brain function in older adults.

“Hippocampal and Cerebral Blood Flow after Exercise Cessation in Master Athletes” by Alfonso J. Alfini, Lauren R. Weiss, Brooks P. Leitner, Theresa J. Smith, James M. Hagberg and J. Carson Smith in Frontiers in Aging Neuroscience. Published online August 5 2016 doi:10.3389/fnagi.2016.00184

Source: Max Planck Institute.

Ludwig II of Bavaria is a particularly striking example of how differently people’s internal clocks can tick. Historical sources tell us that the monarch usually carried out his government business at night and slept during the day. Whether the “Fairy Tale King” had a disorder that disrupted his sleep-wake rhythm is a matter even Gregor Eichele can only speculate about. Nevertheless, Eichele and his team at the Max Planck Institute for Biophysical Chemistry in Göttingen have gained many new insights into how our body’s natural timekeepers work.

“The sleep-wake cycle is intimately linked with our internal clock,” says Gregor Eichele, who heads the Genes and Behaviour Department of the Max Planck Institute in Göttingen. Eichele knows first-hand how the internal clock can affect wellbeing: for many years he commuted regularly between Germany and the USA, and the circadian clock has long been one of his scientific passions.

Every day, millions of people experience how their sleep patterns are affected by their internal clock. Nowadays air passengers can cross several time zones within hours. The result is that their internal clock often gets out of synch. Others complain of sleep disturbances when the clocks are turned forward or back by just one hour for summer and winter time. Even in the case of such small adjustments, it can take the internal clock several days to re-synchronize with the environment so that the affected individual is able to sleep again as usual.

“Nevertheless, sleep and the internal clock are fundamentally different. Whereas sleep is a function of the body as a whole, the internal clock is a property of individual cells,” Eichele emphasizes. At the same time, the two influence each other. For example, neurons and substances like oxytocin and other sleep-regulating neuropeptides are controlled by the 24-hour circadian clock, which is therefore essential to ensure that we’re able to fall asleep at the right time.

The word “circadian” is derived from the Latin circa (approximately) and diem (day). It expresses the fact that the internal clock only approximately keeps a 24-hour rhythm. An individual can have a circadian clock with a rhythm of, say, 24.7 hours. If the person lived for several weeks in a room that is always illuminated, he or she would fall sleep 42 minutes later every day than on the previous day. Environmental conditions – mainly light – act as timekeepers to continuously recalibrate the internal clock to a rhythm of exactly 24 hours.

This seemingly complex system exists because the daily day-night cycle is not in itself sufficient to synchronize the biological processes in our body. Consider, for example, the light environment of modern life. If our physiological rhythms were merely a response to the presence or absence of light, any prolonged evening with all its artificial light sources would have catastrophic effects on our metabolism and sleep-wake rhythm. Instead, our internal clock recognizes these external time signals as spurious and keeps the body chronologically stable.

The circadian clock probably arose at the very dawn of evolution. The very first single-celled organisms in the primordial seas may have benefited from an ability to predict the sunrise and descend into deeper waters to avoid it. In this way they escaped from the UV radiation of the sun, which at the time was still essentially unfiltered. In the darkness of the deep sea, the clock then signalled to the microbes when it was time to surface again.

Once they evolved, virtually all life forms have retained the internal circadian clock movement. It is beneficial for plants to carry out photosynthesis only during the day. In diurnal mammals such as humans, body temperature rises before waking. The release of the stress hormone cortisol peaks in the morning to boost physical and mental performance. Metabolism, muscle tone, renal function and blood metabolite concentrations fluctuate over the course of a day.

There is a molecular clock for every cell, every tissue, every organ − whether the liver, kidneys, heart, gut, immune system or skin – and for the body as a whole. “We have a whole shop full of clocks,” says Eichele. Being Swiss, you might say he is predestined to analyze such mechanisms. In order for all the clocks to display the same time, they must be continuously synchronized with the 24-hour light / dark cycle of the environment.

The most important clock, the suprachiasmatic nucleus (SCN), is located in the brain. Within this nucleus are 50,000 interlinked neurons that are also connected to neurons in other brain regions. The SCN receives signals through nerve fibres from specialized sensory cells in the eyes. When light strikes a light-sensitive pigment in the sensory cells of the retina, they generate an electrical signal, which is relayed to the SCN.

Without the SCN, hamsters, for example, lose their daily rhythm. Scientists have measured this by placing a treadmill in the cage and recording the rotations of the wheel as a measure of the hamsters’ activity. Hamsters are mainly active between sunset and sunrise. Without an SCN, however, they were about as likely to exercise during the day as during the night. Yet the animals did not sleep more than usual.

This finding suggests that the nucleus, as the master clock, relays information to all the other clocks in the cells, tissues and organs of the body, and synchronizes them both with the day and with each other. However, this theory has been called into question by recent research: Eichele’s team has modified mice genetically in such a way that the important clock gene Bmal1 is inactive specifically in the SCN. Their experiments differ from the hamster studies in that the connections to and from the nucleus are left intact. According to the theory, the animals’ internal clocks should go haywire.

That doesn’t happen! “We’ve found that the other circadian clocks remain synchronized even without the master clock in the SCN,” Eichele explains – at least under the condition that light and dark alternate in a 24-hour rhythm. Chaos ensues, however, if mice lacking the SCN clock are kept in permanent darkness. They then have problems keeping their other internal clocks in synch.

The body therefore needs the natural light-dark cycle as a timekeeper. Although food intake can calibrate the circadian clock to a precise 24-hour rhythm, this results in only semi-synchronized internal clocks. Evidently, the clock system is organized like a federal country that is able to keep the individual regional governments running even if the federal government sometimes grows weak. “This system is ultimately more stable than one that relies exclusively on the SCN,” Eichele says.

But how do internal clocks synchronize without the master pacemaker in the brain? One possibility is that the body’s clocks receive light/dark information from the SCN. Researchers have shown that light can activate clock genes in organs such as the liver via the autonomous nervous system.

If the nucleus is absent, light signals travelling from the eyes into the body also peter out. Light then no longer has an effect on the autonomous nervous system or the body’s clocks. Since the scientists from Göttingen only switch off a single clock gene and not the entire neural nucleus, light signals are still able to reach and synchronize the other clocks in the body via the nucleus. Evidently, the signals do not have to be pre-processed in the clock cells of the nucleus.

It is also possible, however, that other important clocks in the brain stand in for the SCN and synchronize the body’s clocks. A likely candidate would be the pituitary gland, which also receives light signals from the eyes. Located at the base of the brain, the gland releases the hormone ACTH into the bloodstream, which is then transported to the adrenal glands, where it triggers the release of cortisol, adrenalin and noradrenalin.

These stress hormones are known to be important pacemakers for the internal clocks of peripheral organs. Eichele and his team have discovered that mice with a defective SCN clock rhythmically release the hormone corticosterone in the course of the day in synch with other body clocks – almost as in normal mice. This hormone is analogous to cortisol in humans. “It’s possible that corticosterone synchronizes the body’s clocks if the SCN fails as a timekeeper,” Eichele concludes. This suggests that the internal clock in the adrenal glands is almost as important as the clock in the SCN.

Moreover, the clocks in the body’s tissues and organs are influenced not only by light but also by sleep. “You have to be relaxed, free of stress and able to sleep when you want, meaning in accordance with one’s personal chronotype, which determines whether you go to bed early or late and tend to sleep for short or long periods,” says Henrik Oster of the University of Lübeck, who headed a research group at the Max Planck Institute in Göttingen until the end of 2012.

Since Oster’s time in Göttingen, he and his colleagues have been studying the relationships between sleep, the internal clock and metabolism. They have observed, for example, that the liver and fat cells of mice with sleep disorders no longer operate in sync. The researchers want to determine if the rhythm of the cells of other organs, such as the kidneys, is also decoupled.

A lot of evidence also suggests that sleep disorders can also alter metabolism via the internal clock. For example, Oster and his colleagues at the Max Planck Institute altered the normal sleep rhythm of mice, thus compromising their internal clocks. They prevented the mice from sleeping in the morning by placing toys in their cages. After a few days, they found that the disrupted sleep pattern had an impact on the internal clocks of peripheral organs, which were then no longer able to switch important metabolic genes on and off.

One target of such a metabolic disturbance is hormone-sensitive lipase. Normally the circadian system ensures that this adipocyte enzyme is active during the sleep phase. It then breaks down stored fats, which the body needs to bridge this period without food. However, because lipase activity is lower in sleep disorders, little fat is released into the body. “Because blood glucose levels fall in these circumstances, the result is an energy emergency. The animals get hungry,” Oster says. The mice start to eat, which then further disrupts their sleep patterns. The result is a vicious circle that causes the animals to gain more and more weight. To complicate matters, hormones in the stomach reset the liver’s clock if the mice eat when they should actually be asleep. Consequently, the liver’s metabolism becomes increasingly imbalanced.

Is the body somehow able to compensate for this metabolic chaos? The answer is yes, in some circumstances. Oster’s team disturbed sleeping mice and only provided access to food during their normal waking phase. The mice were then allowed to eat as much as they wanted. “That normalized activation of the clock genes in the liver,” Oster says. This indicates that the time of food intake appears to be a very important factor for the development of obesity and metabolic diseases.”

The Lübeck-based researchers have also observed that clock genes regulate metabolic changes in sleep-deprived humans. Whether that really can lead to obesity and diabetes has not been established. However, studies on shift workers also point in that direction.

The mouse experiments also clearly show that properly synchronized sleep and food intake can compensate for – and perhaps even reverse – many metabolic imbalances. For this and other reasons, Oster believes that stabilizing the internal rhythm can be an important factor in the treatment of metabolic diseases. After all, many metabolic functions follow a pronounced daily rhythm and are influenced by stress. Sleep, for example plays a key role. “If you get sufficient sleep at the right time,” Oster says, “you’ll be less susceptible to metabolic disorders.”

In a nutshell

Sleep and the internal clock are closely associated with each other: if the internal clock gets out of synch, sleep problems can develop. And individuals who sleep poorly or irregularly disrupt their internal clock. Cells and organs also follow their own internal clock. The suprachiasmatic nucleus, a cluster of neurons in the brain, is the master pacemaker for other clocks in the body. However, the latter can also function without the nucleus. Some of them receive light/dark information directly from the eyes. Sleep defects can trigger metabolic disorders by altering the activity of clock genes, thereby disrupting downstream metabolic processes.

Source: Gregor Eichele – Max Planck Institute
Image Source: NeuroscienceNews.com images are credited to MPI for Biophysical Chemistry / Regina Faubel / Hartmut Sebesse / Boettcher-Gajewsk.

Summary: Running helps to produce a molecule that can heal myelin in mice, a new study reports.

Source: Ottawa Hospital Research Institute.

Researchers at The Ottawa Hospital and the University of Ottawa have discovered that a molecule triggered by running can help repair certain kinds of brain damage in animal models. They found that this molecule, called VGF nerve growth factor, helps to heal the protective coating that surrounds and insulates nerve fibres. Their study, published in Cell Reports, could pave the way for new treatments for multiple sclerosis and other neurodegenerative disorders that involve damaged nerve insulation.

“We are excited by this discovery and now plan to uncover the molecular pathway that is responsible for the observed benefits of VGF,” said Dr. Picketts, senior author of the paper and a senior scientist at The Ottawa Hospital and professor at the University of Ottawa. “What is clear is that VGF is important to kick-start healing in damaged areas of the brain.”

The team made this discovery while studying mice genetically modified to have a small cerebellum, the part of the brain that controls balance and movement. These mice had trouble walking and lived only 25 to 40 days.

However, if these mice were given the opportunity to run freely on a wheel, they lived over 12 months, a more typical mouse lifespan. The running mice also gained more weight and acquired a better sense of balance compared to their sedentary siblings. However, they needed to keep exercising to maintain these benefits. If the running wheel was removed, their symptoms came back and they did not live as long.

Looking at their brains, the researchers found that the running mice gained significantly more insulation in their cerebellum compared to their sedentary siblings.

To find out why running was causing this insulation, the team looked for differences in gene expression between the running and sedentary mice and identified VGF as a prime candidate. VGF is one of the hundreds of molecules that muscles and the brain release into the body during exercise. It also has an anti-depressant effect that helps make exercise feel good.

When the research team used a non-replicating virus to introduce the VGF protein into the bloodstream of a sedentary mutant mouse, the effects were similar to having the mouse run – more insulation in the damaged area of the cerebellum, and fewer disease symptoms.

“We saw that the existing neurons became better insulated and more stable,” said Dr. Matías Alvarez-Saavedra, the lead author on the paper. “This means that the unhealthy neurons worked better and the previously damaged circuits in the brain became stronger and more functional.”

Dr. Alvarez-Saavedra obtained his PhD in Dr. Picketts’ research group, and is currently a postdoctoral fellow at the New York University School of Medicine and the Howard Hughes Medical Institute.

“We need to do broader research to see whether this molecule can also be helpful in treating multiple sclerosis and other neurodegenerative diseases,” said Dr. Picketts.

Funding: This study was funded by the Canadian Institutes of Health Research, with support from The Ottawa Hospital Foundation. The group has now received funding from the MS Society of Canada and the Canadian Partnership for Stroke Recovery to further investigate VGF. Dr. Picketts is also a member of the University of Ottawa Brain and Mind Research Institute. Dr. Alvarez-Saavedra is funded by a Pew Latin American Postdoctoral Fellowship in the Biomedical Sciences.

Source: Amelia Buchanan – Ottawa Hospital Research Institute 
Image Source: NeuroscienceNews.com image is in the public domain
Original Research: Full open access research for “Voluntary Running Triggers VGF-Mediated Oligodendrogenesis to Prolong the Lifespan of Snf2h-Null Ataxic Mice” by Matías Alvarez-Saavedra, Yves De Repentigny, Doo Yang, Ryan W. O’Meara, Keqin Yan, Lukas E. Hashem, Lemuel Racacho, Ilya Ioshikhes, Dennis E. Bulman, Robin J. Parks, Rashmi Kothary, and David J. Picketts in Cell Reports. Published online October 11 2016 doi:10.1016/j.celrep.2016.09.030

Abstract

Voluntary Running Triggers VGF-Mediated Oligodendrogenesis to Prolong the Lifespan of Snf2h-Null Ataxic Mice

Highlights
•Running promotes the survival of mice with cerebellar ataxia following Snf2h inactivation
•Running ataxic mice show enhanced oligodendrogenesis and de novo myelination
•Comparative RNA-seq studies identify VGF as a contributor to brain repair
•VGF overexpression improves ataxic phenotype in mice without exercise

Summary
Exercise has been argued to enhance cognitive function and slow progressive neurodegenerative disease. Although exercise promotes neurogenesis, oligodendrogenesis and adaptive myelination are also significant contributors to brain repair and brain health. Nonetheless, the molecular details underlying these effects remain poorly understood. Conditional ablation of the Snf2h gene impairs cerebellar development producing mice with poor motor function, progressive ataxia, and death between postnatal days 25–45. Here, we show that voluntary running induced an endogenous brain repair mechanism that resulted in a striking increase in hindbrain myelination and the long-term survival of Snf2h cKO mice. Further experiments identified the VGF growth factor as a major driver underlying this effect. VGF neuropeptides promote oligodendrogenesis in vitro, whereas Snf2h cKO mice treated with full-length VGF-encoding adenoviruses removed the requirement of exercise for survival. Together, these results suggest that VGF delivery could represent a therapeutic strategy for cerebellar ataxia and other pathologies of the CNS.

“Voluntary Running Triggers VGF-Mediated Oligodendrogenesis to Prolong the Lifespan of Snf2h-Null Ataxic Mice” by Matías Alvarez-Saavedra, Yves De Repentigny, Doo Yang, Ryan W. O’Meara, Keqin Yan, Lukas E. Hashem, Lemuel Racacho, Ilya Ioshikhes, Dennis E. Bulman, Robin J. Parks, Rashmi Kothary, and David J. Picketts in Cell Reports. Published online October 11 2016 doi:10.1016/j.celrep.2016.09.030

Summary: A new study reports 20 minutes of moderate exercise can act as an anti-inflammatory. The findings could be beneficial for those with inflammatory diseases such as fibromyalgia and arthritis.

Source: UCSD.

One moderate exercise session has a cellular response that may help suppress inflammation in the body.

It’s well known that regular physical activity has health benefits, including weight control, strengthening the heart, bones and muscles and reducing the risk of certain diseases. Recently, researchers at University of California San Diego School of Medicine found how just one session of moderate exercise can also act as an anti-inflammatory. The findings have encouraging implications for chronic diseases like arthritis, fibromyalgia and for more pervasive conditions, such as obesity.

The study, recently published online in Brain, Behavior and Immunity, found one 20-minute session of moderate exercise can stimulate the immune system, producing an anti-inflammatory cellular response.

“Each time we exercise, we are truly doing something good for our body on many levels, including at the immune cell level,” said senior author Suzi Hong, PhD, in the Department of Psychiatry and the Department of Family Medicine and Public Health at UC San Diego School of Medicine. “The anti-inflammatory benefits of exercise have been known to researchers, but finding out how that process happens is the key to safely maximizing those benefits.”

The brain and sympathetic nervous system — a pathway that serves to accelerate heart rate and raise blood pressure, among other things — are activated during exercise to enable the body to carry out work. Hormones, such as epinephrine and norepinephrine, are released into the blood stream and trigger adrenergic receptors, which immune cells possess.

This activation process during exercise produces immunological responses, which include the production of many cytokines, or proteins, one of which is TNF — a key regulator of local and systemic inflammation that also helps boost immune responses.

“Our study found one session of about 20 minutes of moderate treadmill exercise resulted in a five percent decrease in the number of stimulated immune cells producing TNF,” said Hong. “Knowing what sets regulatory mechanisms of inflammatory proteins in motion may contribute to developing new therapies for the overwhelming number of individuals with chronic inflammatory conditions, including nearly 25 million Americans who suffer from autoimmune diseases.”

The 47 study participants walked on a treadmill at an intensity level that was adjusted based on their fitness level. Blood was collected before and immediately after the 20 minute exercise challenge.

“Our study shows a workout session doesn’t actually have to be intense to have anti-inflammatory effects. Twenty minutes to half-an-hour of moderate exercise, including fast walking, appears to be sufficient,” said Hong. “Feeling like a workout needs to be at a peak exertion level for a long duration can intimidate those who suffer from chronic inflammatory diseases and could greatly benefit from physical activity.”

Inflammation is a vital part of the body’s immune response. It is the body’s attempt to heal itself after an injury; defend itself against foreign invaders, such as viruses and bacteria; and repair damaged tissue. However, chronic inflammation can lead to serious health issues associated with diabetes, celiac disease, obesity and other conditions.

“Patients with chronic inflammatory diseases should always consult with their physician regarding the appropriate treatment plan, but knowing that exercise can act as an anti-inflammatory is an exciting step forward in possibilities,” said Hong.

Study co-authors include Stoyan Dimitrov, and Elaine Hulteng, UC San Diego.

Funding: Funding from American Recovery and Reinvestment Act, National Institutes of Health.

Source: Michelle Brubaker – UCSD
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Inflammation and exercise: Inhibition of monocytic intracellular TNF production by acute exercise via β2-adrenergic activation” by Stoyan Dimitrov, Elaine Hulteng, and Suzi Hong in Brain, Behavior, and Immunity. Published online December 21 2016 doi:10.1016/j.bbi.2016.12.017

Abstract

Inflammation and exercise: Inhibition of monocytic intracellular TNF production by acute exercise via β2-adrenergic activation

Regular exercise is shown to exert anti-inflammatory effects, yet the effects of acute exercise on cellular inflammatory responses and its mechanisms remain unclear. We tested the hypothesis that sympathoadrenergic activation during a single bout of exercise has a suppressive effect on monocytic cytokine production mediated by β2 adrenergic receptors (AR). We investigated the effects of 20-min moderate (65–70% VO2 peak) exercise-induced catecholamine production on LPS-stimulated TNF production by monocytes in 47 healthy volunteers and determined AR subtypes involved. We also examined the effects of β-agonist isoproterenol and endogenous β- and α-agonists epinephrine and norepinephrine, and receptor-subtype-specific β- and α-antagonists on TNF production in a series of in vitro investigations. LPS-stimulated TNF production by peripheral blood monocytes was determined intracellularly by flow cytometry, using an intracellular protein transport inhibitor. Percent TNF-producing monocytes and per-cell TNF production with and without LPS was suppressed by exercise with moderate to large effects, which was reversed by a β2-AR antagonist in spite that plasma TNF levels did not change. This inhibitory response in TNF production by exercise was mirrored by β-AR agonists in an agonist-specific and dose-dependent manner in vitro: similar isoproterenol (EC50 = 2.1–4.7 × 10−10 M) and epinephrine (EC50 = 4.4–10 × 10−10 M) potency and higher norepinephrine concentrations (EC50 = 2.6–4.3 × 10−8 M) needed for the effects. Importantly, epinephrine levels observed during acute exercise in vivo significantly inhibited TNF production in vitro. The inhibitory effect of the AR agonists was abolished by β2-, but not by β1- or α-AR blockers. We conclude that the downregulation of monocytic TNF production during acute exercise is mediated by elevated epinephrine levels through β2-ARs. Decreased inflammatory responses during acute exercise may protect against chronic conditions with low-grade inflammation.

“Inflammation and exercise: Inhibition of monocytic intracellular TNF production by acute exercise via β2-adrenergic activation” by Stoyan Dimitrov, Elaine Hulteng, and Suzi Hong in Brain, Behavior, and Immunity. Published online December 21 2016 doi:10.1016/j.bbi.2016.12.017