BRAIN PLASTICITY: The antidepressant that restores youth to neurons

This "new generation" antidepressant, fluoxetine (Prozac®) could also restore youth to neurons that inhibit aging, reveal this work by the Picower Institute for Learning and Memory, MIT (Cambridge), conducted in mice and published in the Journal of Neuroscience.

Cognitive loss caused more by the loss of plasticity than the loss of cells:

the common belief would indeed be that the loss of neurons linked to cell death could explain functional and cognitive deficiencies related to age. However "this loss is very limited during normal aging and does not explain age-related cognitive decline", explains lead author Ronen Eavri and his colleague Elly Nedivi: "it seems rather that the structural alterations of neuronal morphology and synaptic connections are the factors most correlated with brain age and can therefore be considered the physical basis of age-related decline”.

Demonstration of the cause and its possible reversal:

this work provides new evidence that the decline in this ability of brain cells to evolve, called "plasticity", rather than a decrease in the total number of cells, may be the basis of sensory and cognitive declines associated with normal brain aging . In particular, the scientists show that the age-inhibiting interneurons in the visual cortex of mice remain just as abundant during aging, but that their "branches" become simpler and much less dynamic and structurally flexible. But they also provide proof of concept that it is possible to restore much of the lost plasticity in cells, by giving mice a commonly used antidepressant drug, fluoxetine (the active ingredient in Prozac).

The sudden drop in the “dynamism index”:

in the study, the researchers focused on the aging of inhibitory interneurons, which is less well understood than that of excitatory neurons, but which plays a key role in plasticity—essential for learning and memory and for sensory acuity. The researchers focused on the visual cortex. The team counted and chronically tracked the structure of inhibitory interneurons in dozens of mice aged 3, 6, 9, 12 and 18 months and showed that inhibitory interneurons retained the ability to dynamically remodel into adulthood. , but that on the other hand, the plasticity reaches a limit then decreases gradually from about 6 months. Thus, between 3 and 18 months, the dendrites gradually become simpler, presenting fewer branches and this,

Fluoxetine promotes the remodeling of the branches of the interneuron in mice:

with the addition of the drug in drinking water at the age of 3 months (in green on the lower visual) and for 6 months, 67% of the cells resume new growth at nine months of age, showing that early treatment can reverse the age-related decline in plasticity of neurons in the visual cortex.

This finding, in mice, that fluoxetine can attenuate age-related loss of plasticity suggests considerable hope for a therapeutic approach in reducing sensory and cognitive deficits associated with aging.

A single drop of blood brings cells to attention

Several studies have already attempted to visualize the cellular ballet that starts after an injury and at the start of the healing process. This study from the Universities of Oslo and Eindhoven shows how a single drop of blood induces skin cells to align, and how this first connection between cells precedes a much more pronounced collective and coordinated cell migration, spanning distances micrometric or even millimetric. Data that gives rise here, in the journal Nature Communications, to the development of a simulation model that opens up new perspectives on the mechanisms of healing.

What happens to skin cells when they encounter blood?

The team from Oslo University Hospital carried out experiments on blood-deprived cells, which were subsequently exposed to blood serum. Remarkably, the experiment shows that all cells begin to move and migrate in the same direction, that of the blood serum.

Each of us will sustain approximately 10,000 injuries in our lifetime, ranging from minor cuts to traumatic wounds or surgical wounds. In most cases, the wounds heal, but in some cases the healing process is faulty and leads to the development of a chronic wound. In particular during aging and in the event of certain pathologies including diabetes and obesity.

Blood plays an important and independent role in wound healing :

Different molecular components of blood trigger tissue repair processes after injury. Here, researchers are looking at what happens when dormant skin cells come into contact with blood when no wound is present. Blood serum alone induces spontaneous movement (migration) and growth (proliferation) of cells, 2 essential processes or phases in wound healing. Cell divisions are polarized and align with the direction of cell migration, a valuable new insight or knowledge for tissue repair. In short, the presence of blood serum is sufficient to activate dormant skin cells into a migratory and proliferative state and the wound edge,

A “connectivity” also takes place between the cells and whereas the cells which remain disconnected or isolated only follow random individual movements, strong connectivities between cells take place, resulting in a much more pronounced collective and coordinated cell migration. , covering distances of several millimeters.

A digital simulation model is thus developed by these scientists, which imitates the shape and movement of cells in the presence and absence of blood. In this model, cells deprived of blood remain quiescent, while the addition of blood activates the cells and sets them in motion. Simulations indicate that enhanced cell-cell connectivity causes cells to align more tightly with their neighbors, giving rise to the large-scale collective motion observed in previous experiments.

Inflammation and increased blood flow to the wound site can be activated without having an open wound , for example by bruising. The scientists believe that their results may be relevant in this area: “ It can be assumed, based on these new data, that cell migration is also activated in these situations.

In fact, our skin cells are said to be much more active and dynamic than previously thought and that this skin dynamic here regulated by blood can also occur in many other situations ”.

The next step will be to understand why the presence of blood triggers this cell activity and why cells divide asymmetrically in the direction of cell migration!

OBESITY: Male, female, apple or pear?

If we compare, in terms of obesity, body silhouettes, “pears are healthier than apples”, concludes this study from University of California – Riverside. Data that is addressed here more specifically to each sex: because in women, fat generally accumulates around the hips, giving a pear-shaped silhouette, in men, fat tends to accumulate around abdomen, creating an apple shape. This study presented in the journal Frontiers in Immunology and conducted on mice, concludes that it is healthier to “be” a pear than an apple.

Previous animal studies have shown that females are protected against weight gain when they are young, due to the high presence of estrogen in the ovaries. This finding has led to a better understanding of the risk of weight gain after menopause. This new research, also conducted in mice, finds that after a high-fat diet, male mice show low testosterone levels and decreased sperm count – in addition to neuroinflammation in the brain, not seen in female mice. The team therefore looked at the role of hormones in weight gain and obesity.

Obesity, hormones in males: male mice on a high-fat diet,

develop, like men, a metabolic syndrome (see visual) including type 2 diabetes, insensitivity to insulin and markers of vascular disorders;
store fat deeper (visceral and abdominal fat) which can affect internal organs. Their silhouette is more like the shape of an apple. The accumulated fat then recruits immune cells from the bloodstream which are activated, leading to inflammation. Peripheral immune cells, including macrophages in particular, cross the blood-brain barrier and this infiltration of peripheral immune cells into the brain induces neuroinflammation;
show an almost 50% reduction in their testosterone and sperm levels.

Obesity, hormones in females: female mice on a high-fat diet,

store fat differently than their male counterparts, rather subcutaneously, just under the skin;
their estrogen hormones seem to protect them to some degree from fat accumulation;
they show neither neuroinflammation nor changes in reproductive hormones, suggesting that they are protected by factors other than ovarian estrogen.

The message is therefore aimed at both men and women: “ Watch your diet and keep an eye on your weight and in particular on the accumulation of abdominal fat ”.

Editorial team Santélog

MICROBIOTA: Obesogenic household disinfectants for children

Household cleaning products can contribute to overweight children, reveals this Canadian study presented in the Canadian Medical Association Journal (CMAJ). By modifying the intestinal microbiota of children, these disinfectants disrupt their metabolic balance and thus increase the risk of obesity.

It is the analysis of the intestinal flora of 757 infants aged 3 to 4 months, with regard to their body weight, at 1 and 3 years of age and their exposure to disinfectants and detergents used at home, which leads to these conclusions. Analysis of these data from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort coupled with World Health Organization growth charts shows:

Altered gut microbiota in babies aged 3-4 months most frequently exposed to household disinfectants such as multi-surface cleaners;
these babies show lower levels of Haemophilus and Clostridium bacteria but higher levels of Lachnospiraceae;
levels of Lachnospiraceae bacteria in particular are higher with more frequent cleaning with disinfectants, which is not seen with green cleaners.

Higher levels of Lachnospiracea bacteria: “We find,” comments lead author Dr. Anita Kozyrskyj, professor of pediatrics at the University of Alberta “that children living in homes that use disinfectants at least once times a week are 2 times more likely to have higher levels of Lachnospiracea gut microbes at 3 or 4 months of age. At 3 years old, their body mass index (BMI) is higher. On the other hand, infants from homes that use environmentally friendly cleaners have much lower levels of intestinal microbacteria, enterobacteriaceae”.

Prefer ecological products? The study suggests that using eco-friendly products may be healthier for mothers and also contribute to healthy gut microbiomes and healthy weights in their infants. Experts from Johns Hopkins (Baltimore) comment on these results, calling them biologically plausible.

The authors call for further studies to explore these "microbial-mediated mechanisms."

BLOOD PRESSURE: The surface patch that monitors it in depth

And this patch from the University of California – San Diego monitors blood pressure “deep inside the body”, explains this team from the University of California, San Diego in the journal Nature Biomedical Engineering. A new non-invasive and, above all, continuous monitoring mode that will make it possible to detect cardiovascular problems earlier and with greater precision.

The patch is therefore intended to monitor continuously and in real time variations in blood pressure in patients suffering from heart or lung disease, as well as in patients who are seriously ill or undergoing surgery. The patch uses ultrasound and therefore could be used to non-invasively track other physiological signs from sites inside the body.

Until now, the patches were limited to detecting surface signals or just under the skin. "But it's like looking at just the tip of the iceberg," says researcher Sheng Xu, professor of nanoengineering at UC San Diego. “By integrating ultrasound technology into the patch, we are able to non-invasively pick up many other signals and identify new biological events deep below the surface of the skin. »

The 3rd dimension, depth: it is a 3rd third dimension, the "depth" which is thus added to the detection spectrum of portable electronics, summarizes the author: because the ultrasound patch can continuously monitor blood pressure central in the main arteries at a depth of up to four centimeters under the skin. A technology that will most likely be useful in many hospital procedures, especially of course in cardiovascular surgery, where accurate real-time assessment of central blood pressure is required.

A convenient alternative to current clinical methods: by measuring central blood pressure – which differs from blood pressure measured using an inflated cuff around the arm, or peripheral blood pressure – the device indicates blood pressure that is more accurate and better predictor of heart disease risk. Not to mention the non-invasiveness. Because the measurement of the central arterial pressure is carried out according to:

an invasive clinical method that involves a catheter inserted into a blood vessel in a patient's arm, groin, or neck and guiding it to the heart.
There is also a non-invasive method but its data is less precise: it involves placing a pen-shaped probe, called a tonometer, on the skin directly above a large blood vessel. To get a good reading, the tonometer must be held steady, at the perfect angle, and with the right pressure. The results therefore frequently differ between the tests and the technicians.

This convenient ultrasound patch alternative, soft and stretchy, wearable against the skin and provides accurate central blood pressure readings, tested on a male subject, gives more consistent and accurate recordings than other blood pressure measurement methods. central blood pressure.

Certainly, this patch will have to be improved and tested before reaching clinical practice, but it is already a major advance to have adapted ultrasound technology into a portable platform.

DIETARY FIBER: Calms the brain during aging

Less age-related brain inflammation with regular dietary fiber intake, says this University of Illinois study adds a new health benefit of these nutrients. Here, it is precisely on immune cells in the brain known as microglia that the fibers exert their effects, thus helping to reduce age-related cognitive decline. Benefits documented in the journal Frontiers in Immunology mainly linked to their by-products, short-chain fatty acids including butyrate.

With age, microglia in the brain produce chemicals known to impair cognitive and motor function. It is one of the explanations and causes of the decline of memory and other brain functions in the elderly. This study from the University of Illinois offers a simple and natural remedy, dietary fiber . We knew that they promote the growth of good bacteria in the intestine. When these bacteria digest fiber, they produce short-chain fatty acids (SCFAs), including butyrate.

Understanding how sodium butyrate works: Butyrate has anti-inflammatory properties on microglia and improves memory in mice, previous studies have shown, says Dr. Rodney Johnson, a professor at the University of Illinois. Although positive results of sodium butyrate – the pharmacological form – have been observed in these studies, the mechanism of action remains poorly understood. The study reveals, in aged mice, that butyrate inhibits the production of harmful chemicals by inflamed microglia. One such chemical is interleukin-1β, which is associated with Alzheimer's disease in humans. This being demonstrated, humans cannot directly consume sodium butyrate, so there remains the solution of a diet rich in soluble fiber.

Gut bacteria convert fiber to butyrate naturally . Indeed, butyrate derived from dietary fiber should have the same benefits in the brain as the drug form, yet no one had tested it before. So the researchers fed groups of young and old mice low-fiber and high-fiber diets, then measured blood levels of butyrate and other SCFAs, as well as inflammatory chemicals in the blood. 'intestine. This experience shows that:

a high-fiber diet increases butyrate and other SCFAs in the blood, both in young and older mice;
only old mice show intestinal inflammation with a low-fiber diet;
older mice fed a high-fiber diet had significantly reduced gut inflammation and no gut differences with other age groups. This confirms that dietary fiber can indeed regulate the inflammatory environment in the gut;
examination of signs of inflammation in the brain via the analysis of 50 unique genes in microglia finally shows that the high fiber diet reduces the inflammatory profile in aged animals.

The next step will be to examine the effects of diets on cognition and behavior or the precise mechanisms of the gut-brain axis. And if these data were obtained in mice, the researchers are confident about their generalization to humans.

“ What you eat matters. We know that older people consume 40% less dietary fiber than recommended. Not getting enough fiber could have negative consequences for brain health and inflammation in general .”

MEDICAL CANNABIS: On its broad-spectrum efficacy

This study from the University of New Mexico (Albuquerque) documents the effectiveness of medical cannabis in the treatment of a wide range of health problems, through two studies, presented in the journals Medicines and Frontiers in Pharmacology. Researchers here use a mobile app to identify and track patients' symptom relief and see in the field that medical cannabis immediately relieves dozens of symptoms with relatively minimal side effects.

The team of Jacob Miguel Vigil, Professor of Psychology and Sarah See Stith, Professor of Economics describes the significant therapeutic effects of cannabis both clinically and statistically. Their analysis of data collected with the Releaf application, released in 2016, for educational purposes for patients made it possible to assess in real time the levels of intensity of the symptoms and the side effects of patients consuming medical cannabis. And if the results were extrapolated to the general population, the authors comment, cannabis could replace many multi-billion dollar drugs around the world.

Releaf is an assessment app that allows patients to track and manage their cannabis use decisions under natural conditions, while avoiding disorders associated with excessive use (memory bias, desocialization). Here Releaf allowed researchers to collect massive volumes of patient-entered information around their use and the effects of real cannabis used in real circumstances. A scale impossible to reach with randomized controlled trials.

Main findings:

The first study, covering 27 different medical conditions with symptoms ranging from seizures to depression, shows, with the use of medical cannabis, an average reduction in symptoms of almost 4 points on a scale of 1 to 10;
The second study, conducted specifically on the use of natural cannabis buds and to treat insomnia, also shows a strong level of effectiveness which varies slightly depending on the characteristics of the plant and the method of preparation.
The researchers obviously draw a parallel with prescription drugs with inevitable side effects, which also explains why medical cannabis is rapidly gaining popularity, including among older people and patients suffering from severe chronic diseases.
Finally, their results confirm the numerous studies on the effectiveness of cannabis as a possible treatment for a wide range of medical conditions ranging from post-traumatic stress disorder to cancer, chronic pain, epilepsy or "spasticity". While these studies have already suggested just how great the therapeutic potential of cannabis is, this new analysis is the first to assess the effects of cannabis used daily by millions of people in the United States.

Precisely,

the current results underscore the magnitude of the reduction in symptoms after cannabis use: more than 94% of cannabis users report a reduction in their intensity after "self-administered" cannabis use and in the various medical conditions (disorders sleep, eating disorders including intestinal permeability and adipogenesis, libido and fertility, pain perception, motivation, happiness, anxiety, learning and memory, social functioning, autoimmune responses, cancer); these data suggest the ability of phytocannabinoids to influence the human endocannabinoid system, which regulates both mental and physical health and behavioral systems.
Cannabis use is associated with frequent and numerous, but generally mild, side effects: positive side effects (relaxation, relaxation, well-being) are much more frequently reported than negative side effects (headaches in particular).

According to the authors, cannabis could find a permanent place in our therapeutic toolbox and treat health problems more effectively and safely than conventional pharmaceutical treatments. The most glaring example being the treatment of insomnia. Then there would also be a “significant economic impact”.

" If the benefit-risk ratio of cannabis as identified in the short term in our studies reflects its long-term therapeutic potential, the substitution of cannabis for traditional pharmaceuticals could reduce the risk of drug interactions and the costs associated with taking multiple drugs, allowing patients to treat multiple comorbidities with a single treatment .”

HYPERACTIVITY: What if ADHD announced a risk of Parkinson's?

This team from the University of Utah suggests attention deficit hyperactivity disorder (ADHD) as a key to identifying future risk for Parkinson's disease. While 10-11% of children are diagnosed with ADHD, the very long-term effects of the disorder, and its drug treatment, remain understudied. This team confirms that people with ADHD in childhood have an increased risk of developing Parkinson's disease, much later in life. Preliminary results presented in the journal Neuropsychopharmacology, which at this stage do not call into question the treatment "especially for children who cannot control their symptoms".

Parkinson's disease is generally considered a neurodegenerative disease associated with aging, notes Dr. Glen Hanson, professor of pharmacology and toxicology at the University: "This may be the first time that a childhood disease and its treatment may be linked to a geriatric expression of a neurodegenerative disease”.

This retrospective, population-based study of 31,769 ADHD patients, of whom 4,960 received stimulants and 158,790 ADHD-free control participants matched to the ADHD group on sex and age, finds that:

patients with ADHD are more than twice as likely to develop Parkinson's disease vs people without ADHD during their childhood or adolescence;
the estimated risk is 6 to 8 times higher in ADHD patients who received stimulant treatments, including methylphenidate (Ritalin), amphetamine salts (Adderall), and dexmethylphenidate (Focaline).
The estimate would be that out of 100,000 young people with ADHD followed throughout life, 1 to 2 will develop Parkinson's disease before the age of 50;
out of 100,000 young people treated for ADHD and followed throughout life, 8 to 9 will develop Parkinson's disease before the age of 50;
patients with a more severe type of ADHD may have an increased risk of motor neuron disease.

One possible explanation: ADHD is a brain disorder associated with changes in dopamine release, which regulates emotional response. Parkinson's disease is a progressive disorder of the nervous system associated with tremors, stiffness and slowed movements, itself associated with a deficiency of dopamine.

Results still considered preliminary but which confirm those of previous studies which already suggested a link between the abuse of amphetamine and the onset of Parkinson's disease. And as for the treatment of ADHD, whose effects on the risk of Parkinson's remain to be dissociated, " there always remains an advantage, in particular for children who cannot control their ADHD symptoms ", conclude the researchers, pending additional research.

PARKINSON: Being able to track dopamine in the brain

These tiny sensors, which can track dopamine in the brain for more than a year, will be invaluable in monitoring patients with Parkinson's disease and other neurological diseases. It is an “invention” by a team from the Massachusetts Institute of Technology (MIT) and a feat, because these sensors can remain in place for several months. Monitoring dopamine levels could help doctors deliver stimulation or treatment more selectively, and only when needed.

Dopamine, a signaling molecule used throughout the brain, plays a major role in regulating our mood and controlling movement. Many disorders, including Parkinson's disease, depression and schizophrenia, are linked to dopamine deficiencies. By designing this new means of measuring dopamine in the brain for more than a year, the researchers also hope, beyond the opportunity to better assess the response to treatments, to learn more about the role of dopamine in healthy and diseased brains. “Until then, it was impossible to follow the evolution of its levels, in particular with the clinical evolution of the associated medical conditions”, explains Ann Graybiel, professor at MIT and member of the McGovern Institute for Brain Research. .

Track dopamine over the long term:Dopamine is one of many neurotransmitters that neurons in the brain use to communicate with each other. Traditional systems measuring dopamine-carbon electrodes with a diameter of about 100 microns can only be used reliably for about a day because they induce scar tissue that interferes with the ability of the electrodes to interact with dopamine. . The duration of follow-up was therefore the real challenge for the MIT team. The team designed these tiny sensors about 10 microns in diameter and were able to implant up to 16 of them to measure dopamine levels in different parts of patients' striatum. The main goal was indeed to operate the sensors over a long period of time while "retrieving" daily data on dopamine levels. The challenge was to avoid any immune reaction, in order to avoid the scar tissue that interferes with the accuracy of the readings.

These tiny sensors are virtually invisible to the immune system , even over long periods of time. After implantation of the sensors, populations of microglia (immune cells that respond to short-term damage) and astrocytes, which respond over longer periods of time, are found to be unchanged and similar to that of non-implanted brain tissue. The demonstration is carried out in animals, with 3 to 5 sensors per animal, to a depth of about 5 millimeters, in the striatum. Readings were taken weekly, after stimulating the release of dopamine from the brainstem, which travels to the striatum. This is the first proof of concept of sensors that can operate for more than a few months.

One obvious application: monitoring Parkinson's disease: If developed for use in humans, these sensors could be useful for monitoring patients with Parkinson's disease, especially those receiving deep brain stimulation . This treatment involves implanting an electrode that delivers electrical impulses into a deep structure of the brain. Using a sensor to monitor dopamine levels could help doctors deliver stimulation more selectively, only when needed. Then other sensors could be developed to measure other critical neurotransmitters in the brain.

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