Sport and memory go hand in hand

September 23, 2020

Science Daily/Université de Genève

If sport is good for the body, it also seems to be good for the brain. By evaluating memory performance following a sport session, neuroscientists from the University of Geneva (UNIGE) demonstrate that an intensive physical exercise session as short as 15 minutes on a bicycle improves memory, including the acquisition of new motor skills. How? Through the action of endocanabinoids, molecules known to increase synaptic plasticity. This study, to be read in the journal Scientific Reports, highlights the virtues of sport for both health and education. School programmes and strategies aimed at reducing the effects of neurodegeneration on memory could indeed benefit from it.

Very often, right after a sporting exercise -- especially endurance such as running or cycling -- one feels physical and psychological well-being. This feeling is due to endocannabinoids, small molecules produced by the body during physical exertion. "They circulate in the blood and easily cross the blood-brain barrier. They then bind to specialise cellular receptors and trigger this feeling of euphoria. In addition, these same molecules bind to receptors in the hippocampus, the main brain structure for memory processing," says Kinga Igloi, lecturer in the laboratory of Professor Sophie Schwartz, at UNIGE Faculty of Medicine's Department of Basic Neurosciences, who led this work. "But what is the link between sport and memory? This is what we wanted to understand," she continues.

Intense effort is more effective 

To test the effect of sport on motor learning, scientists asked a group of 15 young and healthy men, who were not athletes, to take a memory test under three conditions of physical exercise: after 30 minutes of moderate cycling, after 15 minutes of intensive cycling (defined as 80% of their maximum heart rate), or after a period of rest. "The exercise was as follows: a screen showed four points placed next to each other. Each time one of the dots briefly changed into a star, the participant had to press the corresponding button as quickly as possible," explains Blanca Marin Bosch, researcher in the same laboratory. "It followed a predefined and repeated sequence in order to precisely evaluate how movements were learnt. This is very similar to what we do when, for example, we learn to type on a keyboard as quickly as possible. After an intensive sports session, the performance was much better."

In addition to the results of the memory tests, the scientists observed changes in the activation of brain structures with functional MRI and performed blood tests to measure endocannabinoid levels. The different analyses concur: the faster individuals are, the more they activate their hippocampus (the brain area of memory) and the caudate nucleus (a brain structure involved in motor processes). Moreover, their endocannabinoid levels follow the same curve: the higher the level after intense physical effort, the more the brain is activated and the better the brain's performance. "These molecules are involved in synaptic plasticity, i.e. the way in which neurons are connected to each other, and thus may act on long-term potentiation, the mechanism for optimal consolidation of memory," says Blanca Marin Bosch.

Improving school learning or preventing Alzheimer's disease 

In a previous study, the research team had already shown the positive effect of sport on another type of memory, associative memory. However, contrary to what is shown here, they had observed that a sport session of moderate intensity produced better results. It therefore shows that, as not all forms of memory use the same brain mechanisms, not all sports intensities have the same effects. It should be noted that in all cases, physical exercise improves memory more than inaction.

By providing precise neuroscientific data, these studies make it possible to envisage new strategies for improving or preserving memory. "Sports activity can be an easy to implement, minimally invasive and inexpensive intervention. For example, would it be useful to schedule a sports activity at the end of a school morning to consolidate memory and improve learning?"

Improving academic learning or preventing Alzheimer's disease 

In a previous study, the research team had already shown the positive effect of sport on another type of memory, associative memory. But, contrary to what is shown here, they had observed that a sport session of moderate intensity, not high intensity, produced better results. Thus, just as not all forms of memory use the same brain mechanisms, not all sports intensities have the same effects. It should be noted that in all cases, physical exercise improves memory more than inaction.

By providing precise neuroscientific data, these studies make it possible to envisage new strategies for improving or preserving memory. "Sports activity can be an easy to implement, minimally invasive and inexpensive intervention. Would it be useful, for example, to plan a moment of sport at the end of a school morning to consolidate school learning," Kinga Igloi wonders, who, with her colleagues at Sophie Schwartz's laboratory, aims to achieve such practical objectives.

Neuroscientists are currently pursuing their work by studying memory disorders, and in particular by studying populations at high risk of developing Alzheimer's disease. "Some people as young as 25 years of age may experience subtle memory deficits characterised by overactivation of the hippocampus. We want to evaluate the extent to which sports practice could help compensate for these early deficits that are precursors to Alzheimer's disease.," conclude the authors.

https://www.sciencedaily.com/releases/2020/09/200923124616.htm

Curbing your enthusiasm for overeating

Mouse study focuses on cannabis-like molecules that augment feeding behavior

June 11, 2019

Science Daily/University of California - Riverside

Signals between our gut and brain control how and when we eat food. But how the molecular mechanisms involved in this signaling are affected when we eat a high-energy diet and how they contribute to obesity are not well understood.

Using a mouse model, a research team led by a biomedical scientist at the University of California, Riverside, has found that overactive endocannabinoid signaling in the gut drives overeating in diet-induced obesity by blocking gut-brain satiation signaling.

Endocannabinoids are cannabis-like molecules made naturally by the body to regulate several processes: immune, behavioral, and neuronal. As with cannabis, endocannabinoids can enhance feeding behavior.

The researchers detected high activity of endocannabinoids at cannabinoid CB1 receptors in the gut of mice that were fed a high-fat and sugar -- or Western -- diet for 60 days. This overactivity, they found, prevented the food-induced secretion of the satiation peptide cholecystokinin, a short chain of amino acids whose function is to inhibit eating. This resulted in the mice overeating. Cannabinoid CB1 receptors and cholecystokinin are present in all mammals, including humans.

Study results appear in the journal Frontiers in Physiology, an open-access journal.

"If drugs could be developed to target these cannabinoid receptors so that the release of satiation peptides is not inhibited during excessive eating, we would be a step closer to addressing the prevalence of obesity that affects millions of people in the country and around the world," said Nicholas V. DiPatrizio, an assistant professor of biomedical sciences in the UCR School of Medicine who led the research team.

DiPatrizio explained that previous research by his group on a rat model showed that oral exposure to dietary fats stimulates production of the body's endocannabinoids in the gut, which is critical for the further intake of high-fat foods. Other researchers, he said, have found that levels of endocannabinoids in humans increased in blood just prior to and after eating a palatable high-energy food, and are elevated in obese humans.

"Research in humans has shown that eating associated with a palatable diet led to an increase in endocannabinoids -- but whether or not endocannabinoids control the release of satiation peptides is yet to be determined," said Donovan A. Argueta, a doctoral student in DiPatrizio's lab and the first author of the research paper.

Previous attempts at targeting the cannabinoid CB1 receptors with drugs such as Rimonabant -- a CB1 receptor blocker -- failed due to psychiatric side effects. However, the DiPatrizio lab's current study suggests it is possible to target only the cannabinoid receptors in the gut for therapeutic benefits in obesity, greatly reducing the negative side effects.

The research team plans to work on getting a deeper understanding of how CB1 receptor activity is linked to cholecystokinin.

"We would also like to get a better understanding of how specific components of the Western diet -- fat and sucrose -- lead to the dysregulation of the endocannabinoid system and gut-brain signaling," DiPatrizio said. "We also plan to study how endocannabinoids control the release of other molecules in the intestine that influence metabolism."

https://www.sciencedaily.com/releases/2019/06/190611081915.htm

Endocannabinoids, Closely Related to Active Ingredients in Cannabis Plant, Can Promote Pain

https://www.sciencedaily.com/images/2009/09/090911212404_1_540x360.jpg

September 14, 2009

Science Daily/ETH Zurich

The endocannabinoids occurring naturally in the human body are closely related to the active ingredients of the cannabis plant. Cannabis has been used for thousands of years, for example to treat chronic pain. However, the fact that the endocannabinoids produced by the body itself can also be involved in the origin of pain is the astonishing result of studies by a Zurich research team.

The first mention of cannabis as a medicinal plant was in the Chinese book of medicinal plants “Shennong bencao jing”, which is almost 5000 years old. The Chinese emperor Shennong is said to have recommended cannabis resin as a remedy for various illnesses. After the use of its active ingredients for thousands of years to alleviate chronic pain, a study by the research group led by Hanns Ulrich Zeilhofer, Professor at the Institute of Pharmaceutical Sciences at ETH Zurich and the Institute of Pharmacology and Toxicology at the University of Zurich now shows that the endocannabinoids produced by the body itself can lead to pain sensitisation in certain types of pain. Their study was recently published in the scientific journal Science.

Short-circuit in the spinal cord

Pain and touch are conducted to the brain through the spinal cord via two different systems. This enables the brain to distinguish between pain and simple touch. However, because the two systems are interconnected via nerve fibres in the spinal cord, simple touches can also be perceived as pain, for example as a result of a “short circuit”. Such faulty circuits can occur if inhibitory chemical messengers (neurotransmitters) in the spinal cord are absent or blocked. Zeilhofer says, “This happens in various illnesses and can even be triggered by intense pain stimuli themselves.”

The body’s own endocannabinoids play a considerable part in the biochemical processes taking place in this, as the study by Zeilhofer and his team shows. In particular, the release of endocannabinoids in the spinal cord seems to be responsible for the fact that, after an initial pain stimulus, pain sensitivity spreads beyond the area originally stimulated. Even slight touch in this area is then perceived as painful. The endocannabinoids thus cause a “short circuit” between the touch signals and pain.

The scientists tested the theory that endocannabinoids released in the spinal cord during intense pain stimuli are responsible for this short-circuit. It actually became apparent that activating the endocannabinoid receptors on isolated spinal cord reduced the release of pain-inhibiting neurotransmitters. Animals that had developed the expected oversensitivity to slight touching after a pain stimulus behaved normally again after their cannabinoid receptors in the spinal cord were blocked.

Endocannabinoid inhibitors relieve pain

The fact that these processes also occur in humans was shown by experiments on healthy volunteers carried out in the Anaesthesiology Department at the University of Erlangen. Pain receptors in the volunteers’ skin were locally stimulated with an electric current, after which the size of the area hypersensitive to pain was determined. In the next step, half of the volunteers received a placebo for ten days, while the others were given Rimonabant, a substance that blocks certain cannabinoid receptors. The experiment was then repeated. Zeilhofer says, “The painful area formed in the test subjects whose endocannabinoid receptors had been blocked was about fifty percent smaller than in those who had taken the placebo.”

Helpful to the pharmaceutical industry

However, further experiments also showed that other forms of pain, e.g. those occurring as a result of nerve injuries, developed normally in mice that lacked endocannabinoid receptors. The endocannabinoids seem to play no major pain promoting role in this case. Zeilhofer says, “In the next step we want to find out which pain patients might possibly benefit from blocking the cannabinoid receptors. At any rate our findings should be of great interest to drug companies who are working with this pain model to develop new analgesics.”

https://www.sciencedaily.com/releases/2009/09/090911212404.htm

New Antidepressant Drug Increases 'Brain's Own Cannabis'

December 13, 2005

Science Daily/McGill University

Researchers have discovered a new drug that raises the level of endocannabinoids -- the 'brain's own cannabis' -- providing anti-depressant effects. The new research published in this week's Proceedings of the National Academy of Sciences (PNAS), suggests the new drug, called URB597, could represent a safer alternative to cannabis for the treatment of pain and depression, and open the door to new and improved treatments for clinical depression--a condition that affects around 20% of Canadians.

In preclinical laboratory tests researchers found that URB597 increased the production of endocannabinoids by blocking their degradation, resulting in measurable antidepressant effects. "This is the first time it has been shown that a drug that increases endocannabinoids in the brain can improve your mood," says the lead investigator Dr. Gabriella Gobbi, an MUHC and Université de Montréal researcher.

Endocannabinoids are chemicals released by the brain under certain conditions, like exercise; they stimulate specific brain receptors that can trigger feelings of well-being. The researchers, which included scientists from the University of California at Irvine, were able to measure serotonin and noradrenaline activity as a result of the increased endocannabinoids, and also conducted standard experiments to gauge the 'mood' of their subjects and confirm their findings.

"The results were similar to the effect we might expect from the use of commonly prescribed antidepressants, which are effective on only around 30% of the population," explains Dr. Gobbi. "Our discovery strengthens the case for URB597 as a safer, non-addictive, non-psychotropic alternative to cannabis for the treatment of pain and depression and provides hope for the development of an alternate line of antidepressants, with a wider range of effectiveness."

Cannabis has been known for its anti-depressant and pain-relief effects for many years, but the addictive nature and general health concerns of cannabis use make this drug far from ideal as a medical treatment. The active ingredient in cannabis--THC (Tetrahydrocannabinol)--stimulates cannabinoid receptors.

Funding for this study was provided by the Fonds de la Recherche en Santé du Québec (FRSQ), the Canadian Psychiatric Research Foundation (CPRF), the National Institute on Drug Abuse (NIDA) and an MUHC fellowship.

https://www.sciencedaily.com/releases/2005/12/051213172852.htm

How CBD, a component in marijuana, works within cells

February 11, 2015

Science Daily/Stony Brook University

A team of Stony Brook University researchers have identified fatty acid binding proteins (FABPs) as intracellular transporters for two ingredients in marijuana, THC and CBD (cannabidiol). The finding, published early online in the Journal of Biological Chemistry, is significant because it helps explain how CBD works within the cells. Recent clinical findings have shown that CBD may help reduce seizures and could be a potential new medicine to treat pediatric treatment-resistant epilepsy.

CBD differs from THC in that it is not psychoactive and does not bind to cannabinoid receptors. Some children who are resistant to conventional antiepileptic drugs have been reported to show improvement with oral CBD treatment. The Stony Brook research team found that three brain FABPs carry THC and CBD from the cell membrane to the interior of the cell. This action enabled them to conduct experiments inhibiting FABPs and thereby reducing anandamide breakdown inside the cells.

"Anandamide, an endocannabinoid, has been shown to have neuroprotective effects against seizures in basic research studies and this may turn out to be a key mechanism of seizure control," explained Dale Deutsch, PhD, Professor of Biochemistry and Cell Biology and a faculty member of the Institute of Chemical Biology and Drug Discovery at Stony Brook University. "Therefore by CBD inhibiting FABPs, we could potentially raise the levels of anandamide in the brain's synapses."

The findings in the paper, titled "Fatty Acid Binding Proteins are Intracellular Carriers for THC and CBD," stem from the team's research that spans five years and includes their discoveries that showed anandamide levels were raised in rodent brains using novel drugs targeted to FABPs. In 2013, they received a $3.8 million grant from the National Institute on Drug Abuse, part of the National Institutes of Health (NIH), to target endocannabinoid transporters to develop drugs for pain and inflammation.

The current research involving FABPs as transporters of CBD involves the work of faculty and students from several Stony Brook Departments. The team includes four Professors -- Dr. Deutsch, Martin Kaczocha (Anesthesiology), Iwao Ojima (Chemistry and the Institute of Chemical Biology and Drug Discovery), and Stella Tsirka (Pharmacological Sciences). The team also features a post-doctoral fellow (Jeremy Miyauchi in Pharmacological Sciences), a researcher who recently received his PhD (William Berger in Chemistry), a graduate student Matthew Elmes, a research technician Liqun Wang, and undergraduate students Brian Ralph, Kwan-Knok Leung, and Joseph Sweeney, all from the Department of Biochemistry and Cell Biology.

https://www.sciencedaily.com/releases/2015/02/150211140914.htm

Hibernating hamsters could provide new clues to Alzheimer's disease

February 6, 2019

Science Daily/American Chemical Society

Syrian hamsters are golden-haired rodents often kept as house pets. Cold and darkness can cause the animals to hibernate for three to four days at a time, interspersed with short periods of activity. Surprisingly, the hibernation spurts of these cute, furry creatures could hold clues to better treatments for Alzheimer's disease (AD), according to a recent study.

When hamsters and other small mammals hibernate, their brains undergo structural and metabolic changes to help neurons survive low temperatures. A key event in this process appears to be the phosphorylation of a protein called tau, which has been implicated in AD. In the brains of hibernating animals, phosphorylated tau can form tangled structures similar to those seen in AD patients. However, the structures disappear and tau phosphorylation is rapidly and fully reversed when the hibernating animal wakes up. Coral Barbas and colleagues wondered if determining how hibernating hamsters' brains clear out the tangled proteins could suggest new therapies for AD.

So the researchers used mass spectrometry to analyze metabolic changes in Syrian hamster brain before (control), during and after hibernation. A total of 337 compounds changed during hibernation, including specific amino acids, endocannabinoids and brain cryoprotectants. In particular, a group of lipids called long-chain ceramides, which could help prevent oxidative damage to the brain, were highly elevated in hibernating animals compared with those that had recently woken up. The largest change for any metabolite -- about 5-fold more in hibernating animals compared with control animals -- was for phosphatidic acid, which is known to activate an enzyme that phosphorylates tau. The Syrian hamster is an excellent model to study substances that could help protect neurons, the researchers say.

The authors acknowledge funding from the Spanish Ministry of Economy and Competitiveness, the Network Center for Biomedical Research in Neurodegenerative Diseases and the San Pablo CEU University Foundation.

https://www.sciencedaily.com/releases/2019/02/190206104607.htm