Mice With a Healthy Gut Microbiome Are More Motivated to Exercise

reposted from https://www.the-scientist.com/news-opinion/mice-with-a-healthy-gut-microbiome-are-more-motivated-to-exercise-70845?utm_campaign=TS_DAILY_NEWSLETTER_2022&utm_medium=email&_hsmi=238698979&_hsenc=p2ANqtz-_ymMGFDXk8FwZj9ol6Ge0rVxC-_oiDn4m4ofgcFD6cZlpoxtOelPBFQEdpq6BDv4MMh_wFge2mwPYQOnZ3Dz61bMwgUQ&utm_content=238698979&utm_source=hs_email Mice With a Healthy Gut Microbiome Are More Motivated to Exercise A neural pathway between the gut and the brain led to the release of dopamine when the mice ran on a wheel or treadmill, but only in the presence of a robust microbiome. a white mouse sits on a blue exercise wheel, looking out onto the shavings below A black and white headshot of Katherine Irving Katherine Irving Dec 16, 2022 | 4 min read PDF VERSION ABOVE: © ISTOCK.COM, MARY SWIFT The gut is a jungle teeming with microorganisms that are instrumental to the process of digesting food, regulating metabolism, and defending against infection. However, research now suggests yet another way that the gut microbiome’s influence extends far past the bounds of its abdominal home. In mice, gut bacteria stimulate the production of dopamine during exercise, without which the mice lack the motivation to continue running, scientists at the University of Pennsylvania reported December 14 in Nature. “This is the most comprehensive study I have ever seen,” says Theodore Garland Jr., an evolutionary physiologist studying the gut-brain axis in mice at the University of California, Riverside, who wasn’t involved in the research. “[It’s] pulling together lots of different pieces that we knew before in different contexts or in isolation of other parts in a way that hasn’t been done before.” Exercise is “the single most effective lifestyle intervention that we have that protects us from a very large range of diseases,” says study coauthor Christoph Thaiss, a microbiologist at the University of Pennsylvania Perelman School of Medicine. Yet despite being a very physical activity, he says the success of an individual’s attempts to exercise often depends on their mental state. “If you look at what elite athletes say, many of them will say that they are not necessarily physically better than their competitors, but their mind is very well prepared,” he says. “But when it comes to preparing athletes, mentally or motivationally, for their competitions, there’s very little scientific evidence of how these methods might work.” Previous research had already found that the gut microbiome can influence muscle tissue and cardiovascular fitness as well as brain chemistry. But Thaiss aimed to bring such findings together and examine the broader role of the gut microbiome in exercise performance. So, he and his colleagues set up an experiment using 199 outcrossed mice from eight different genetic backgrounds to ensure that any findings weren’t limited to one strain. Using multiple antibiotics, the researchers altered the mice’s microbiome communities: some mice had fully functioning microbiomes, while the others had their gut microbiomes either partially or entirely removed. See “Tinkering with Gut Microbes Boosts Brain Plasticity in Mice” They then tested each mouse’s performance while running in two different settings: a treadmill, on which the mice were forced to run for an extended period to test their endurance, and a wheel, on which the mice were allowed to run as often and for as long as they wanted. Although all the mice were equally capable of moving around their cages, the mice with reduced microbiomes tired more quickly when exercising on the treadmill than mice with robust microbiomes. They also spent less time on the wheel, which the researchers attributed to reduced motivation to exercise. Thaiss then searched for a neural explanation for the behavioral differences among the groups of mice. He and his team used RNA sequencing to analyze the mice’s striatal spiny neurons, which are involved in producing the behavior-reinforcing neurotransmitter dopamine both before and after exercise, and found that many of the genes normally expressed during exercise were dampened without the microbiome. When he performed an experiment limiting dopamine production during exercise by inhibiting these neurons, it had the same effect that limiting or entirely removing the microbiome had in the previous experiment. From these experiments, Thaiss inferred that the production of dopamine was a significant factor in a mouse’s propensity to exercise, and that a mouse’s gut microbiome composition played some role in the regulation of dopamine in its brain. That led him to conclude that the mice lacking gut bacteria didn’t experience the dopamine rush animals usually get through exercise, known as the “runner’s high.” “If we can remote[ly] control the brain from the perspective of the GI tract, then this becomes a much more accessible problem.” —Christoph Thaiss, University of Pennsylvania Perelman School of Medicine The question then became how microbes in the gut influence dopamine in the brain. To find out, the team inhibited a set of neurons that connects the gastrointestinal tract to the brain using formulated drugs. In the same wheel and treadmill experiments as before, mice with healthy microbiomes but inhibited gut-brain neurons exhibited reduced exercise rates on par with the mice with limited microbiomes, suggesting that it was the stimulation of these neurons that controlled the amount the mice exercised. Finally, the researchers treated mice with specific antibiotics to determine what kinds of microbes were triggering the neurons. They performed a metabolomics analysis to determine which bacterial metabolites triggered the neural response. They found that metabolites known as fatty acid amides (FAAs) made by some microbes found in a healthy mouse gut were the most active during exercise. These FAAs generate neurotransmitters known as endocannabinoids. The scientists performed more experiments using ingestible inhibitors to determine that the endocannabinoids produced by the bacteria’s FAAs were stimulating receptors in the GI tract neurons during exercise, thereby triggering the neurons that subsequently stimulated dopamine production in the brain. “It was really elegant the way they structured the entire story,” says Francesca Ronchi, an immunologist at the Institute of Microbiology, Infectious Diseases and Immunology in Berlin, Germany who wasn’t involved in the study. She adds that she was very impressed by the thoroughness of the paper. “You couldn’t do it better.” Thaiss says that the next step will be to take this research from mice to humans and determine whether the same pathway exists in us. Garland explains that analyzing motivation in humans is more complicated than it is in mice: a person’s incentive to exercise is based on many more factors, including external ones such as their social environment and influence from family or friends, than is a mouse’s. “We don’t go and give our mice pep talks when they run a lot on the wheel,” he observes. In humans, by contrast, those that are naturally talented at some form of exercise may receive more praise, fueling them to exercise more. See “Regular Exercise Helps Patients Combat Cancer” Nonetheless, Ronchi says findings like these could one day reveal ways to stimulate exercise in those who need it, including cancer, Parkinson’s, or Alzheimer’s patients, for whom exercise is a valuable tool in mitigating symptoms. After all, if such a pathway does exist in people, gut microbes may be easier to manipulate or influence than neurons in the brain, Thaiss suggests: Unlike neurons, which are finicky and often inaccessible, gut bacteria could be influenced by an ingestible treatment. “If we can remote[ly] control the brain from the perspective of the GI tract, then this becomes a much more accessible problem,” he says. “But that’s still science fiction for now.” Keywords: bacteriaexercisefitnessgut bacteriagut microbiotaimmunologymicrobiologymicrobiomemicrobiotamouse studyneural activationneuronneurotransmittersNewspathwaysignaling pathwaysstudy story

 reposted from CBC radio - thanks Karolina for this one!

3 ways to boost your memory, according to brain experts

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From exercise to word games with others, these activities reduce your chances of dementia

Amina Zafar · CBC Radio · Posted: Jun 12, 2022 7:36 AM ET | Last Updated: June 12

A couple dances during the festivities of San Cayetano, the patron saint of labour and bread, in Madrid, Spain, last August. Activities like dance, which combine exercise, socializing and cognition, benefit our brains, a psychologist says. (Andrea Comas/The Associated Press)

Worries about dementia often rank high in polls of Canadians' health concerns, but a neurologist says there are ways to keep our cherished memories strong.

Dr. Sandra Black, a cognitive neurologist at Sunnybrook Health Sciences Centre in Toronto, says with normal aging, short-term memory dulls and the brain's processing speed slows with each decade after 50.

To help counter those declines, Black looks for ways to boost memory that are supported by scientific evidence.

1. Get moving

Exercise, from walking to running, is one memory booster that's backed by more and more research. Canada's guidelines recommend at least 150 minutes of moderate to vigorous physical activity per week for adults.

"When you are aerobically exercising, when you're on that run, your muscles are actually releasing a signal. It's called irisin," Black said. "You're actually stimulating the part of the brain that stores information and learns things."

The recent discovery of the irisin protein builds on other research linking muscle and brain function, Black told Dr. Brian Goldman, host of  CBC's podcast The Dose. 

Dr. Sandra Black encourages walking and more heart-pumping physical activity as beneficial for mental abilities like memory and language. (Submitted by Sandra Black)

When she sees patients, Black said she talks about why lifestyle choices such as exercise are important. Since a healthy brain needs a lot of oxygen, whatever protects our blood vessels, heart and circulation, also fuels the brain.

Black and other experts encourage walking, or more heart-pumping physical activities, for their benefits to cognitive abilities like memory and language.

2. Eat the good stuff

Black suggests eating a Mediterranean diet rich in green, leafy vegetables like broccoli, kale and cabbage, as well as berries, whole grains, walnuts and fatty fish such as salmon, mackerel and tuna rich in omega-3 fatty acids.

The advice is based on studies that followed people in different populations that seemed to have a lower prevalence of Alzheimer's and vascular disease, compared with populations following other eating patterns.

The Dose20:41What can I do to boost my memory?

What else works? In one published clinical trial, researchers showed that medium-chain triglycerides found primarily in coconut oil may help delay worsening Alzheimer's disease compared with taking a sugar pill, the gold standard regulators use to approve medications.

Your best bet is to consume healthy nutrients through a varied diet of mostly whole foods, not supplements that promise those benefits in pill form.

Black said patients who can take supplements aren't told to stop if they can afford them, but her team doesn't endorse them, either. That's because the scientific evidence in favour of many supplements fails to take the placebo effect into account, or the trials weren't long enough to measure an effect, she said.

WATCH | More praise for Mediterranean diet:

More praise for Mediterranean diet

4 years ago

Duration2:26

3. Enjoy word games with others

Penny Pexman, a psychology professor at the University of Calgary who studies cognitive neuroscience, suggests activities that combine exercise, socializing and cognition.

Pexman's lab focuses on how we process language, including a study titled This is your brain on Scrabble. 

Scrabble players who enjoy the game and its social benefits are motivated to score higher, Pexman said. 

Aside from the social benefits of getting together to play, Pexman's research suggests competitive Scrabble players also recognize words faster than those who didn't routinely put down tiles, particularly for words presented vertically.

"My best recommendation, based on what I know, is to engage in things like dance or pickleball," Pexman said. "You've got things that involve some spatial skills, they're taxing your working memory and they're also giving you social …benefits, too." 

Pickleball is a workout for both spatial skills and working memory that also offers social benefits. (Brian Blanco/The Associated Press Images for Humana)

Why it's not all downhill

Pexman also studies age-related changes, and notes that many, but not all, cognitive abilities start to decline by about age 30. 

"There are things, though, that you can continue to grow," Pexman said. "Your vocabulary grows throughout your life."

• Exercise, not pills, better at preventing dementia

• Bilingualism boosts the brain at all ages

Black also points to the wisdom and knowledge we gain with age.

"You have a little more trouble with the word finding, but you know a lot more about the world," Black said. 

A 25-year-old may be faster, but a wise elder in many societies has a richer understanding of culture from their life experience, she added.

ABOUT THE AUTHOR

Amina Zafar

Journalist

Amina Zafar covers medical sciences and health topics, including COVID-19 and other infectious diseases, for CBC News. She holds an undergraduate degree in environmental science and a master's in journalism.

Exercise, Stress Resilience, and Locus Ceruleus Galanin

 reposted from SfN

Full paper

https://www.jneurosci.org/content/40/39/7464

Exercise, Stress Resilience, and Locus Ceruleus Galanin

Rachel P. Tillage, Genevieve E. Wilson, L. Cameron Liles, Philip V. Holmes, and David Weinshenker

(see pages 7464–7474)

Regular exercise improves mood and cognition, reduces stress, and increases resilience to subsequent stressors. These effects are mediated by multiple signaling pathways that affect synaptic plsticity and neuronal health in several brain areas. Much evidence suggests that exercise promotes stress resilience by increasing production of the neuropeptide galanin in the locus ceruleus, a structure that drives stress responses by releasing norepinephrine throughout the brain. Galanin is expressed in most locus ceruleus neurons, and it can inhibit spontaneous spiking in noradrenergic neurons. Notably, chronic exercise increases galanin levels in the locus ceruleus of rats, and intracerebroventricular infusion of a galanin antagonist blocks the ability of exercise to increase stress resilience. Moreover, intracerebroventricular infusion of galanin increases stress resilience in rats. Because intracerebroventricular treatments can affect galanin signaling in many brain areas, including hypothalamic nuclei involved in stress responses, Tillage et al. examined the effects of overexpressing galanin selectively in noradrenergic neurons in mice.

The authors first confirmed that 3 week access to a running wheel increased exercise, galanin expression, and stress resilience in mice. Indeed, mice ran 10–16 km/d by the third week of wheel access, and galanin expression in the locus ceruleus of these mice was higher than in sedentary controls. Notably, locus ceruleus galanin levels were correlated with the amount of running and with levels of anxiety-like behavior after footshock stress. In particular, whereas stress caused sedentary mice to spend less time in the open arms of an elevated zero maze the next day, it had no effect on mice that had exercised. Importantly, overexpressing galanin in noradrenergic neurons replicated the effects of exercise—preventing stress-induced increases in anxiety-like behavior in the elevated zero maze—but had no effect on baseline behavior or on acute responses to footshock. Finally, optogenetic activation of the locus ceruleus replicated the effects of footshock stress, and overexpressing galanin in the locus ceruleus blocked this effect.

These data strengthen the hypothesis that increases in galanin expression in the locus ceruleus mediate the effect of exercise on stress resilience. Whether this effect stems from suppression of noradrenergic neuronal activity, effects on locus ceruleus target regions, or both should be examined in future studies.

Footnotes

• This Week in The Journal was written by Teresa Esch, Ph.D.

REPOSTED FROM frontiers blog

Leg exercise is critical to brain and nervous system health

Posted on June 7, 2018 in Featured News, Neuroscience

The study provides new insights into why patients with neurological diseases rapidly decline once movement is limited. Image: Shutterstock

In a new take on the exercise truism ‘use it, or lose it,’ researchers show neurological health is an interactive relationship with our muscles and our world

— By Rachael Bishop

Groundbreaking research shows that neurological health depends as much on signals sent by the body’s large, leg muscles to the brain as it does on directives from the brain to the muscles. Published in Frontiers in Neuroscience, the study fundamentally alters brain and nervous system medicine — giving doctors new clues as to why patients with motor neuron disease, multiple sclerosis, spinal muscular atrophy and other neurological diseases often rapidly decline when their movement becomes limited.

“Our study supports the notion that people who are unable to do load-bearing exercises — such as patients who are bed-ridden, or even astronauts on extended travel — not only lose muscle mass, but their body chemistry is altered at the cellular level and even their nervous system is adversely impacted,” says Dr. Raffaella Adami from the Università degli Studi di Milano, Italy.

The study involved restricting mice from using their hind legs, but not their front legs, over a period of 28 days. The mice continued to eat and groom normally and did not exhibit stress. At the end of the trial, the researchers examined an area of the brain called the sub-ventricular zone, which in many mammals has the role of maintaining nerve cell health. It is also the area where neural stem cells produce new neurons.

Limiting physical activity decreased the number of neural stem cells by 70 percent compared to a control group of mice, which were allowed to roam. Furthermore, both neurons and oligodendrocytes — specialized cells that support and insulate nerve cells — didn’t fully mature when exercise was severely reduced.

The research shows that using the legs, particularly in weight-bearing exercise, sends signals to the brain that are vital for the production of healthy neural cells, essential for the brain and nervous system. Cutting back on exercise makes it difficult for the body to produce new nerve cells — some of the very building blocks that allow us to handle stress and adapt to challenge in our lives.

“It is no accident that we are meant to be active: to walk, run, crouch to sit, and use our leg muscles to lift things,” says Adami. “Neurological health is not a one-way street with the brain telling the muscles ‘lift,’ ‘walk,’ and so on.”

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Related: Exercise in early life has long-lasting benefits

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The researchers gained more insight by analyzing individual cells. They found that restricting exercise lowers the amount of oxygen in the body, which creates an anaerobic environment and alters metabolism. Reducing exercise also seems to impact two genes, one of which, CDK5Rap1, is very important for the health of mitochondria — the cellular powerhouse that releases energy the body can then use. This represents another feedback loop.

These results shed light on several important health issues, ranging from concerns about cardio-vascular impacts as a result of sedentary lifestyles to insight into devastating diseases, such as spinal muscular atrophy (SMA), multiple sclerosis, and motor neuron disease, among others.

“I have been interested in neurological diseases since 2004,” says co-author Dr. Daniele Bottai, also from the Università degli Studi di Milano. “The question I asked myself was: is the outcome of these diseases due exclusively to the lesions that form on the spinal cord in the case of spinal cord injury and genetic mutation in the case of SMA, or is the lower capacity for movement the critical factor that exacerbates the disease?”

This research demonstrates the critical role of movement and has a range of potential implications. For example, missions to send astronauts into space for months or even years should keep in mind that gravity and load-bearing exercise play an important role in maintaining human health, say the researchers.

“One could say our health is grounded on Earth in ways we are just beginning to understand,” concludes Bottai.

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Original article: Reduction of Movement in Neurological Diseases: Effects on Neural Stem Cells Characteristics

REPUBLISHING GUIDELINES: Open access and sharing research is part of Frontiers’ mission. Unless otherwise noted, you can republish articles posted in the Frontiers news blog — as long as you include a link back to the original research. Selling the articles is not allowed.

reposted from G&M

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For children, exercise may help stave off depression

DAVE MCGINN

The Globe and Mail

Published Thursday, Feb. 02, 2017 12:31PM EST

Last updated Wednesday, Feb. 08, 2017 10:41AM EST

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One more reason to make your kids put down screens and go play outside.

Multiple studies have found a link between physical activity and lower rates of depression in adults and teens. Now, researchers have shown the same correlation exists for children as young as 6.

In a study published in this month’s journal Pediatrics, researchers at the Norwegian University of Science and Technology tracked nearly 800 children for two years, beginning when they were six years old.

The children’s parents were interviewed about their children’s mental health. Accelerometers were used to measure each child’s physical activity.

Consistent with previous studies of adults and teenagers, the researchers found that two years later, the physically active kids had fewer symptoms of depression.

“This is important to know, because it may suggest that physical activity can be used to prevent and treat depression already in childhood,” Silje Steinsbekk, associate professor in the Norwegian University of Science and Technology department of psychology, said in a release. While physical activity that makes a kid sweaty or out of breath was linked with a decreased likelihood of showing depressive symptoms, the researchers found no evidence to suggest that having signs of depressive symptoms leads to inactivity.

The conclusion parents should draw from the study is clear, the researchers say: don’t only limit a kid’s screen time. They need to be getting moderate to vigorous physical activity.

In Canada, the more reasons there are to encourage kids to play, and to give caregivers an extra nudge to get them out the door, the better.

Clearly, the message isn’t resonating for a majority of children across the country, despite the fact that there is already ample evidence for the many benefits of physical activity, from lowering the risk of developing Type 2 diabetes to boosting their self-esteem.

A mere 9 per cent of Canadian kids between the ages of 5 and 17 get the recommended one hour of heart-pumping physical activity each day, according to ParticipAction’s latest report card on physical activity for children and youth. Although this new study from Norway was only able to prove a correlation between physical activity and depression, not causation, it is still one more reason on a long and growing list of why we should all be doing our best to make sure children spend more time playing.

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