How Exercise Reduces Belly Fat in Humans

NEUROSCIENCE NEWS   DECEMBER 27, 2018
Source: Cell Press.

According to researchers, interleukin 6 plays a critical role in how exercise helps to reduce body fat.

This graphical abstract shows that in abdominally obese people, exercise-mediated loss of visceral adipose tissue mass requires IL-6 receptor signaling. NeuroscienceNews.com image is credited to Wedell-Neergaard, Lehrskov, and Christensen, et al. / Cell Metabolism.

Some of you may have made a New Year’s resolution to hit the gym to tackle that annoying belly fat. But have you ever wondered how physical activity produces this desired effect? A signaling molecule called interleukin-6 plays a critical role in this process, researchers report December 27 in the journal Cell Metabolism.

As expected, a 12-week intervention consisting of bicycle exercise decreased visceral abdominal fat in obese adults. But remarkably, this effect was abolished in participants who were also treated with tocilizumab, a drug that blocks interleukin-6 signaling and is currently approved for the treatment of rheumatoid arthritis. Moreover, tocilizumab treatment increased cholesterol levels regardless of physical activity.

“The take home for the general audience is ‘do exercise,'” says first author Anne-Sophie Wedell-Neergaard of the University of Copenhagen. “We all know that exercise promotes better health, and now we also know that regular exercise training reduces abdominal fat mass and thereby potentially also the risk of developing cardio-metabolic diseases.”

Abdominal fat is associated with an increased risk of not only cardio-metabolic disease, but also cancer, dementia, and all-cause mortality. Physical activity reduces visceral fat tissue, which surrounds internal organs in the abdominal cavity, but the underlying mechanisms have not been clear. Some researchers have proposed that a “fight-or-flight” hormone called epinephrine mediates this effect. But Wedell-Neergaard and co-senior study author Helga Ellingsgaard of the University of Copenhagen suspected that interleukin-6 could also play an important role because it regulates energy metabolism, stimulates the breakdown of fats in healthy people, and is released from skeletal muscle during exercise.

To test this idea, the researchers carried out a 12-week, single-center trial in which they randomly assigned abdominally obese adults to four groups. A total of 53 participants received intravenous infusions of either tocilizumab or saline as a placebo every four weeks, combined with no exercise or a bicycle routine consisting of several 45-minute sessions each week. The researchers used magnetic resonance imaging to assess visceral fat tissue mass at the beginning and end of the study.

In the placebo groups, exercise reduced visceral fat tissue mass by an average of 225 grams, or 8 percent, compared with no exercise. But tocilizumab treatment eliminated this effect. In the exercise groups, tocilizumab also increased visceral fat tissue mass by approximately 278 grams compared with placebo. In addition, tocilizumab increased total cholesterol and “bad” low-density-lipoprotein (LDL) cholesterol compared with placebo, in both the exercise and no-exercise groups. “To our knowledge, this is the first study to show that interleukin-6 has a physiological role in regulating visceral fat mass in humans,” Wedell-Neergaard says.

The authors note that the study was exploratory and not intended to evaluate a given treatment in a clinical setting. To complicate matters, interleukin-6 can have seemingly opposite effects on inflammation, depending on the context. For example, chronic low-grade elevations of interleukin-6 are seen in patients with severe obesity, type 2 diabetes, and cardiovascular disease. “The signaling pathways in immune cells versus muscle cells differ substantially, resulting in pro-inflammatory and anti-inflammatory actions, so interleukin-6 may act differently in healthy and diseased people,” Wedell-Neergaard explains.

In future studies, the researchers will test the possibility that interleukin-6 affects whether fats or carbohydrates are used to generate energy under various conditions. They will also investigate whether more interleukin-6, potentially given as an injection, reduces visceral fat mass on its own. “We need a more in-depth understanding of this role of interleukin-6 in order to discuss its implications,” Wedell-Neergaard says.

In the meantime, the authors have some practical holiday exercise tips. “It is important to stress that when you start exercising, you may increase body weight due to increased muscle mass,” Wedell-Neergaard says. “So, in addition to measuring your overall body weight, it would be useful, and maybe more important, to measure waist circumference to keep track of the loss of visceral fat mass and to stay motivated.”

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Funding: This study was funded by TrygFonden.

Source: Carly Britton – Cell Press

Publisher: Organized by NeuroscienceNews.com.

Image Source: NeuroscienceNews.com image is credited to Wedell-Neergaard, Lehrskov, and Christensen, et al. / Cell Metabolism.

Original Research: Abstract for “Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial” by Wedell-Neergaard, Lehrskov, and Christensen, et al. in Cell Metabolism. Published December 27 2018.

doi:10.1016/j.cmet.2018.12.007

Abstract

Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial

Visceral adipose tissue is harmful to metabolic health. Exercise training reduces visceral adipose tissue mass, but the underlying mechanisms are not known. Interleukin-6 (IL-6) stimulates lipolysis and is released from skeletal muscle during exercise. We hypothesized that exercise-induced reductions in visceral adipose tissue mass are mediated by IL-6. In this randomized placebo-controlled trial, we assigned abdominally obese adults to tocilizumab (IL-6 receptor antibody) or placebo during a 12-week intervention with either bicycle exercise or no exercise. While exercise reduced visceral adipose tissue mass, this effect of exercise was abolished in the presence of IL-6 blockade. Changes in body weight and total adipose tissue mass showed similar tendencies, whereas lean body mass did not differ between groups. Also, IL-6 blockade increased cholesterol levels, an effect not reversed by exercise. Thus, IL-6 is required for exercise to reduce visceral adipose tissue mass and emphasizes a potentially important metabolic consequence of IL-6 blockade.

https://neurosciencenews.com/exercise-belly-fat-10391/

How lights could restore limb movement

December 27, 2018 By Danielle Kirsh

Researchers at Massachusetts Institute of Technology have used an optogenetic technique to create limb movement and treat muscle tremor in people who have had spinal cord injuries or neurological diseases.

The technique works by activating nerves that express proteins using light. It can be adjusted in real-time using motion cues from the limb. The researchers suggest that the technique could produce smoother limb movement than other electrical systems that are typically used to stimulate nerves in spinal cord injury patients.

This optogenetic technique has so far only been tested in animals, but the researchers suggest that it could be used to restore movement in patients with paralysis in the future. It could also treat unwanted movements that happen with Parkinson’s disease.

“Most people are using optogenetics as sort of a tool to learn about neural circuits, but very few are looking at it as a clinically translatable therapeutic tool as we are,” said Shriya Srinivasan, a researcher on the project, in a press release.

Applications for the technology include restoring motion in paralyzed limbs and powering prosthetics. Optogenetic systems can also restore limb sensation, turn off unwanted pain signals or treat spastic or rigid muscle movements from neurological diseases, according to the researchers.

“Artificial electrical stimulation of muscle often results in fatigue and poor controllability. In this study, we showed a mitigation of these common problems with optogenetic muscle control,” Hugh Herr, lead researchers, said. “This has great promise for the development of solutions for patients suffering from debilitating conditions like muscle paralysis.”

Electrical stimulation of nerves has been clinically used to treat treating, bowel, bladder and sexual dysfunction in spinal cord injury patients. It has also improved muscle conditioning in people who have muscular degenerative diseases and can control paralyzed limbs and prosthetics.

In typical electrical stimulation, electrical pulses are sent to nerve fibers called the axons where muscle movement is triggered by the fibers. This electrical stimulation can quickly fatigue muscles and can be painful, according to the researchers. It can also be hard to target precisely.

Optogenetic stimulation uses nerves that have been genetically engineered to express light-sensitive algae proteins known as opsin. The proteins are what controls electrical signals like nerve impulses. Exposing them to certain wavelengths of light can turn them on and off.

The researchers have engineered mice and rats to express opsins in the leg to control the up and down movement of the ankle joints when switching on an LED light attached over the skin or implanted in the leg.

The closed-loop system is able to change its stimulation in response to signals from the nerves they are activating. In the rodents, the different cues included the ankle joint angle and changes in the length of muscle fibers. The researchers say that the system observes and reduces error in real-time.

Tests of technique also showed that optogenetic stimulation could lead to less fatigue during cyclic motion when compared to electrical stimulation. Electrical systems have large-diameter axons that are activated first with large, oxygen-hungry muscles before smaller axons and muscles. Optogenetics works by stimulating smaller axons before moving on to the bigger fibers.

“When you’re walking slowly, you’re only activating those small fibers, but when you run a sprint, you’re activating the big fibers,” Srinivasan said. “Electrical stimulation activates the big fibers first, so it’s like you’re walking but you’re using all the energy it requires to do a sprint. It’s quickly fatiguing because you’re using way more horsepower than you need.”

The light stimulated system also had a different pattern than electrical systems.

“When we kept doing these experiments, especially for extended periods of time, we saw this really interesting behavior,” Srinivasan said. “We’re used to seeing systems perform really well, and then fatigue over time. But here we saw it perform really well, and then it fatigued, but if we kept going for longer, the system recovered and started performing well again.”

Opsin activity cycles in the nerves resulted in the unexpected rebound, allowing the system to regenerate, according to the researchers.

The researchers plan to test the system further to find the best ways to deliver light to nerves deep in the body while also finding ways to express opsin in human nerves safely and efficiently.

“There are already some 300 trials using gene therapy, and a few trials that use opsin today, so it’s likely in the foreseeable future,” Srinivasan said.

The study was published in the journal Nature Communications and was funded by the MIT Media Lab Consortium.

https://www.medicaldesignandoutsourcing.com/how-limb-movement-could-be-restored-using-light/

HomeFeatured: Your Brain Rewards You Twice Per Meal Neuroscience News

NEUROSCIENCE NEWS   DECEMBER 27, 20

Source: Cell Press.

Summary: Upon eating, dopamine is released in the brain at two different times, during ingestion and when the food reaches our stomach, researchers report.

Suppression of gut-induced release could potentially cause overeating of highly desired food items. NeuroscienceNews.com image is in the public domain.

We know a good meal can stimulate the release of the feel-good hormone dopamine, and now a study in humans from the Max Planck Institute for Metabolism Research in Germany suggests that dopamine release in the brain occurs at two different times: at the time the food is first ingested and another once the food reaches the stomach. The work appears December 27 in the journal Cell Metabolism.

“With the help of a new positron emission tomography (PET) technique we developed, we were not only able to find the two peaks of dopamine release, but we could also identify the specific brain regions that were associated with these releases,” says senior author Marc Tittgemeyer (@tittgemeyer), head of the Institute’s Translational Neurocircuitry Group.

 “While the first release occurred in brain regions associated with reward and sensory perception, the post-ingestive release involved additional regions related to higher cognitive functions.”

In the study, 12 healthy volunteers received either a palatable milkshake or a tasteless solution while PET data were recorded. Interestingly, the subjects’ craving or desire for the milkshake was proportionally linked to the amount of dopamine released in particular brain areas at the first tasting. But the higher the craving, the less delayed post-ingestive dopamine was released.

“On one hand, dopamine release mirrors our subjective desire to consume a food item. On the other hand, our desire seems to suppress gut-induced dopamine release,” says Heiko Backes, group leader for Multimodal Imaging of Brain Metabolism at the Institute, who is co-first author on the study with Sharmili Edwin Thanarajah.

Suppression of gut-induced release could potentially cause overeating of highly desired food items. “We continue to eat until sufficient dopamine was released,” Backes says but adds that this hypothesis remains to be tested in further studies.

Earlier experiments have demonstrated gut-induced dopamine release in mice, but this is the first time it has been shown in humans.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Funding: This research was funded the German Research Foundation in the Transregional Collaborative Research Center and the German Centre for Diabetes Research.

Source: Carly Britton – Cell Press

Publisher: Organized by NeuroscienceNews.com.

Image Source: NeuroscienceNews.com image is in the public domain.

Original Research: Abstract for “Food Intake Recruits Orosensory and Post-ingestive Dopaminergic Circuits to Affect Eating Desire in Humans” by Sharmili Edwin Thanarajah, Heiko Backes, Alexandra G. DiFeliceantonio, Kerstin Albus, Anna Lena Cremer, Ruth Hanssen, Rachel N. Lippert, Oliver A. Cornely, Dana M. Small, Jens C. Brüning, and Marc Tittgemeyer in Cell Metabolism. Published December 27 2018.

doi:10.1016/j.cmet.2018.12.006

Abstract

Food Intake Recruits Orosensory and Post-ingestive Dopaminergic Circuits to Affect Eating Desire in Humans

Pleasant taste and nutritional value guide food selection behavior. Here, orosensory features of food may be secondary to its nutritional value in underlying reinforcement, but it is unclear how the brain encodes the reward value of food. Orosensory and peripheral physiological signals may act together on dopaminergic circuits to drive food intake. We combined fMRI and a novel [11C]raclopride PET method to assess systems-level activation and dopamine release in response to palatable food intake in humans. We identified immediate orosensory and delayed post-ingestive dopamine release. Both responses recruit segregated brain regions: specialized integrative pathways and higher cognitive centers. Furthermore, we identified brain areas where dopamine release reflected the subjective desire to eat. Immediate dopamine release in these wanting-related regions was inversely correlated with, and presumably inhibited, post-ingestive release in the dorsal striatum. Our results highlight the role of brain and periphery in interacting to reinforce food intake in humans.

https://neurosciencenews.com/meal-brain-reward-10390/

Treatment of Parkinson's disease: Separating hope from hype

26-Dec-2018

The article by Dr. Alireza Mohammadi et al. is published in Current Gene Therapy, Volume 18, Issue 4, 2018

Bentham Science Publishers

Parkinson's disease is a neurodegenerative disorder characterized by motor and nonmotor deficits majorly caused by the loss of dopaminergic cells in the Substantia Nigra pars compacta (SNc) as well as the destruction of nigrostriatal pathway. Despite the numerous advances in cutting-edge approaches for the treatment or prevention of PD, there still exists some obstacles that have incapacitated the definitive treatment of this disease. 

New therapeutic strategies have emerged over recent years to treat PD, including gene- and stem cell- based therapies, targeted delivery of neurotrophic factors, and brain stimulation techniques such as Transcranial Magnetic Stimulation (TMS), transcranial Direct Current Stimulation (tDCS), and Deep Brain Stimulation (DBS). 

The review covers various gene therapy strategies including Adeno-Associated Virus-Glutamic Acid Decarboxylase (AAV-GAD), AAV-Aromatic L-Amino Acid Decarboxylase (AAV-AADC), Lenti-AADC/Tyrosine Hydroxylase/Guanosine Triphosphate- Cyclohydrolase I (Lenti-AADC/TH/GTP-CH1), AAV-Neurturin (AAV-NRTN), α-Synuclein silencing, and PRKN gene delivery. The review also covers the advantages and disadvantages of these treatments along with the results of relevant trials. With many advances in treatments for PD, there still exist some hurdles that have resulted in treatment failure; the reasons for failure of treatment were described, with hope separated from hype.

                                                             ###

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Researchers at the Medical School explore novel ways to target Parkinson’s disease

By Nisha Dabhi | 12/27/2018

Team of researchers and clinicians examine the effects of using focused ultrasound technology as an alternative treatment for Parkinson’s disease

Team of researchers and clinicians examine the effects of using focused ultrasound technology as an alternative treatment for Parkinson’s disease

Researchers at the Medical School have found that using focused ultrasound technology — a non-invasive type of brain surgery — can reduce tremor symptoms in some Parkinson’s disease patients while also improving quality of life. 

Parkinson’s disease is a progressive neurological disorder that affects movement by impacting the dopamine-producing neurons in a part of the brain known as the substantia nigra. Dopamine is a neurotransmitter — a chemical substance transmitted from one neuron to another — that is known to be involved in movement.

The specific symptoms of this disorder vary from patient to patient. While some experience behavioral symptoms such as tremors, slowed movement, muscle rigidity and impaired balance, others also see changes in mood and cognition, especially in later stages of the disease when other brain pathways may be affected. 

Due to the heterogeneity of the disease, there is no single treatment, and its causes remain unknown. The fact that Parkinson’s disease affects the brain poses another challenge for researchers and clinicians regarding treatment. 

“Unlike things like kidney disease and liver disease, we can’t really take the brain out and put a new one back in,” said Binit Shah, a neurologist at the University Medical Center. “So, I think the amount that we can improve and learn is exponential.”

However, a number of treatments do exist and have been effective for a subset of Parkinson’s disease patients’ symptoms. According to Shah, one of the most conservative treatments — and one of the most important — is physical exercise and activity. 

With patients who have tremor symptoms related to the loss of dopamine-releasing neurons, the medication Levodopa  is used as a treatment, as it can be converted to dopamine and help with movement control. Although the medication can continue to remain effective for later stages of the disease, the disease progression may also develop other symptoms that the medication does not target.

“It may take more medication to get the same effect because the cells that make dopamine may not be functioning well or are degenerating, but also other features of PD can develop like problems with balance, swallowing, cognition, where the problem is not the lack of dopamine but is due to PD spreading to other parts of the brain,” Shah said. 

In cases where medication is not effective, deep brain stimulation, or DBS, has been used. DBS is an invasive procedure in which electrodes are implanted within certain areas of the brain and produce electrical impulses to disrupt irregular signaling. However, not all Parkinson’s patients are candidates for DBS, and some of those who are choose to opt out due to its invasiveness. 

Currently, a team of researchers and clinicians led by University neurosurgeon Jeff Elias — and including Shah and clinical neuropsychologist Scott Sperling — have pioneered the use of a new technology known as focused ultrasound to reduce tremor symptoms in Parkinson’s patients. 

In focused ultrasound, beams of ultrasound waves concentrate on a target with extreme precision and accuracy. This technology has been used to target tumors as well as open up the blood brain barrier — which prevents many treatments from entering the brain — so that medications can effectively enter and target areas in the brain. 

In the study, Parkinson’s disease patients were divided into two groups — one group received the focused ultrasound treatment, while the other did not receive this treatment. The focused ultrasound technology targeted the ventralis intermedius nucleus of the thalamus. 

“The thalamus is segmented into different areas, and one of those areas is a coordination [center] where a lot of motor fibers intercept and there are tremor fibers that can go through,” Shah said. 

While Elias administered the treatment, Shah did motor assessments in collaboration with other institutions without knowledge of the treatment the patient had received. The research found that there was significant reduction in tremor symptoms for the Parkinson’s disease patients who received focused ultrasound treatment. There was not a significant reduction in other symptoms, such as depression. 

At the same time, the researchers found that this focused ultrasound technology is safe and improves the quality of life for Parkinson’s patients. Sperling measured the quality of life of these patients who underwent the procedure over the span of a year. 

“What you do see is that individuals who had treatment had significant improvements in their quality of life, and if you track all the folks over the next years, you continue to see significant improvements in overall quality of life and in areas such as emotional wellbeing,” Sperling said. 

Now, the researchers and clinicians are looking into using focused ultrasound technology in other areas of the brain such as the subthalamic nucleus of the thalamus and the globus pallidus — both areas that research has shown to be potential targets for Parkinson’s disease. They hope to see if there are significant reductions in other motor symptoms as well as improvements in quality of life. 

Nevertheless, the complexity of the disease may continue to require that research produce new treatments for Parkinson’s disease. 

“These surgeries are new and not for everyone. It's important to note that with Parkinson’s disease there are a lot of effective treatments from [a] medication standpoint and DBS, which remains the primary neurosurgical treatment,” Sperling said. “But this is something that is new and could be [an option] for certain individuals but are not standard practice for everyone with Parkinson’s disease.”

http://www.cavalierdaily.com/article/2018/12/researchers-at-the-medical-school-explore-novel-ways-to-target-parkinsons-disease

Bath Middle School student raises money for Parkinson’s through running

 December 26, 2018

Bath Middle School student Lily Wright is raising money for Parkinson’s disease with her passion for running. (Nathan Strout/The Times Record)

BATH – Not many middle schoolers decide to spend their time trying to help cure a disease that affects millions of people. But that’s exactly what Bath Middle School student Lily Wright has done.

The seventh-grade student has gone above and beyond the standard requirements of a class assignment to practice advocacy skills. She has already run one race to raise money for Parkinson’s disease research and plans to run another one on New Year’s Eve. Already she’s raised $580 for the cause.

The impetus for Wright’s fundraising efforts came from an advocacy project assigned by her teacher at Bath Middle School, Maria Newcomb.

“The advocacy project is something I’ve done in the past, but I haven’t done it in the last three years. It’s basically an opportunity for the students to choose any topic related to wellness (and advocate for it), and I always encourage them to choose something they’re passionate about, something they care about,” said Newcomb.

It wasn’t difficult for Wright to think of an area where she had been personally affected by a health issue. Two of Wright’s grandparents have been diagnosed with Parkinson’s.

“It was the first thing that came to my mind,” said Wright. “I was like, ‘You know what? I should do Parkinson’s disease because not everybody knows about that.’”

Parkinson’s is a debilitating disease that affects the central nervous system. Over time, the disease impacts people’s motor skills and can eventually impact their behavior. According to the Parkinson’s Foundation, more than 10 million people are living with the disease worldwide, and 60,000 Americans are diagnosed annually.

“There’s no cure for it,” said Wright. “There’s all these people who don’t have a cure and they’ve lost all their abilities to, like, do all the things they love, like running or working out somewhere.”

Wright said she has already begun to see how the disease has affected her grandparents.

“Over time, I’ve seen their abilities change. A few years ago, my grandmother took me on a trip to the Grand Canyon. She was so able and willing to do that with all of her grandchildren. Then she had a sickness come this August and that kind of made her take a step back,” said Wright. “That kind of made me sad.”

“My grandfather used to play squash. (He doesn’t) have the ability to do that anymore,” she added.

Wright knew what she cared about, but how would she advocate for it?

Students work on their projects one day a week on their project over the course of a semester, explained Newcomb, conducting research on the topic of their choice and developing their approach to advocacy. Some students chose to make a flyer or brochure, while others have written announcements to go out over the intercom. Topics range from raising self-esteem to fundraising for the Midcoast Humane Society.

Wright decided to draw on one of her passions for her advocacy project.

“I love running. I don’t know where I got that from,” said Wright. “I’m not on a track team or anything, (though) I like doing team sports. I do soccer and lacrosse and those involve running a lot.”

In September, Wright ran her first race–a 5K in Camden as part of the Camden Snow Bowl.

With some encouragement from her mother, Wright decided to kick her project up a notch using her love for running. Cutting through the noise of brochures and announcements, Wright set a goal to raise $500 for Parkinson’s research by running a 5K in November. All of the money raised would go to The Michael J. Fox Foundation to be used for Parkinson’s research.

“I thought I was not going to get close to that,” admitted Wright.

Still, Wright was committed to running the race–even though it was pouring rain on race day.

“When my mom told me it was raining, I was like, ‘Eh, whatever,’” said Wright. “She told me I was crazy and I was like, yup.”

Wright finished the race, raising $580 in the process, surpassing her original goal. She even got second place in her age group.

Inspired by that success, Wright has decided to continue running to raise money for Parkinson’s research.

“I immediately went online and asked, ‘What’s the next race I can do? It’s going to be so cold, but I’m doing it!” she said.

On Monday, December 31, she will be participating in the 5K Polar Bear Dip and Dash in Portland. Not only does that race involve running five kilometers in the Maine winter, it culminates in a quick dip into the ice-cold waters of the Atlantic in January. It’s not an activity for the faint-hearted.

“I’m psyched for it,” said Wright.

While that race is ostensibly meant to raise awareness of climate change, Wright will use it as the next step in her journey to raise money for Parkinson’s research.

Those looking to support Wright’s efforts and fund Parkinson’s research can donate at fundraise.michaeljfox.org/tf-2018/LilyfightsPD.

https://www.timesrecord.com/articles/front-page/bath-middle-school-student-raises-money-for-parkinsons-through-running/

Losing neurons is sometimes not all bad

December 27, 2018, Champalimaud Centre for the Unknown

Neurons in red are the unfit neurons that will be killed for the better functioning of the whole brain, marked in blue. Credit: Dina Coelho (CCU)

Current thinking about Alzheimer's disease is that neuronal cell death in the brain is to blame for the cognitive havoc caused by the disease. But a new study suggests that neuronal death may actually be a protective reaction against the disease. This could lead to a complete rethinking of therapeutic approaches to Alzheimer's.

For the first time, scientists at the Champalimaud Centre for the Unknown (CCU) in Lisbon, Portugal, have shown that neuronal cell death in Alzheimer's disease (AD) may actually not be a bad thing—on the contrary, it may be the result of a cell quality control mechanism trying to protect the brain from the accumulation of malfunctioning neurons. Their results, which were obtained using fruit flies that had been genetically modified to mimic the symptoms of human AD, were published in the journal Cell Reports.

The cell quality control mechanism at play is called cell competition. It leads to the selection of the fittest cells in a tissue by enabling a "fitness comparison" between each cell and its neighbors—with the fitter cells then triggering the suicide of less fit ones.

It has been recently shown that cell competition is a normal, powerful anti-aging mechanism in the body in general and in the brain in particular. "In 2015, we discovered that clearing unfit cells from a tissue was a very important anti-aging mechanism to preserve organ function, says Eduardo Moreno, principal investigator of the Cell Fitness lab at the CCU.

His team reasoned that, if these fitness comparisons happened in normal aging, they could also be involved in neurodegenerative diseases associated with accelerated aging, such as Alzheimer's, Parkinson's disease or Huntington's disease, Moreno explains. "This had never been tested," he says. In collaboration with Christa Rhiner's Stem Cells and Regeneration lab at the CCU, they started by testing AD hallmarks in fruit fly models of the disease.

For this, they bred fruit flies that had been genetically manipulated to express in their brain the human amyloid-beta protein, that forms aggregates in the brains of AD patients. The formation of amyloid-β aggregates in the brain is a crucial step in the development of AD.

The transgenic flies displayed symptoms and pathologies similar to those of AD patients: "they showed loss of long-term memory, accelerated aging of the brain and motor coordination problems, all of which got worse with age", specifies Christa Rhiner, whose team studied the cognitive and motor functions of the flies.

The first thing the scientists wanted to do was to see whether in these flies, neuronal death was indeed activated by the process of fitness comparison—in other words, "that the neurons were not dying on their own but being killed by fitter neighbors," Moreno points out.

"When we started, the current view was that neuronal death must be always detrimental. And much to our surprise, we found that neuronal death actually counteracts the disease," says Dina Coelho, first author of the study. What happened was that when she blocked neuronal death in the flies' brain, the insects developed even worse memory problems, worse motor coordination problems, died earlier and their brain degenerated faster.

However, when she boosted the fitness comparison process, thus accelerating the death of unfit neurons, the flies expressing the AD-associated amyloid-beta proteins showed an impressive recovery. "The flies almost behaved like normal flies with regard to memory formation, locomotive behavior and learning," says Rhiner, and this at a time point where the AD flies were already strongly affected.

This means that the anti-aging mechanism in question keeps working well in Alzheimer's disease and shows that, in fact, "the neuronal death protects the brain from more widespread damage and therefore the neuronal loss is not what is bad, it is worse not to let those neurons die", Moreno emphasizes. "Our most important finding is that we have probably been thinking the wrong way about Alzheimer's disease. Our results suggest that neuronal death is beneficial because it removes neurons that are affected by noxious beta-amyloid aggregates from brain circuits, and having those dysfunctional neurons is worse than losing them" Moreno concludes.

The results could have crucial therapeutical implications. "Some molecules have already been identified as potential inhibitors of cell suicide, and some experimental drugs exist, and are being tested which inhibit those inhibitors of cell death, therefore accelerating neuronal death," says Moreno.

But he cautions: "This work has been done in fruit flies." It will be necessary to see, whether these results on neuronal death in Alzheimer's also hold true for humans.

Journal reference: Cell Reports

Provided by: Champalimaud Centre for the Unknown

https://medicalxpress.com/news/2018-12-neurons-bad.html

Kicking, yelling during sleep? Study finds risk factors for violent sleep disorder

December 26, 2018, American Academy of Neurology

Taking antidepressants for depression, having post-traumatic stress disorder or anxiety diagnosed by a doctor are risk factors for a disruptive and sometimes violent sleep disorder called rapid eye movement (REM) sleep behavior disorder, according to a study published in the December 26, 2018, online issue of Neurology, the medical journal of the American Academy of Neurology. The study also found men are more likely to have the disorder.

REM sleep is the dream state of sleep. During normal REM sleep, your brain sends signals to prevent your muscles from moving. However, for people with REM sleep behavior disorder, those signals are disrupted. A person may act out violent or action-filled dreams by yelling, flailing their arms, punching or kicking, to the point of harming themselves or a sleep partner.

"While much is still unknown about REM sleep behavior disorder, it can be caused by medications or it may be an early sign of another neurologic condition like Parkinson's disease, dementia with Lewy bodies or multiple system atrophy," said study author Ronald Postuma, MD, MSc, of McGill University in Montreal, Canada, and a member of the American Academy of Neurology. "Identifying lifestyle and personal risk factors linked to this sleep disorder may lead to finding ways to reduce the chances of developing it."

The study looked at 30,097 people with an average age of 63. Researchers screened participants for a variety of health conditions and asked about lifestyle, behavior, social, economic and psychological factors.

In addition, every participant was asked, "Have you ever been told, or suspected yourself, that you seem to act out your dreams while asleep?"

Researchers then identified 958 people, or 3.2 percent, with possible REM sleep behavior disorder, after excluding participants with Parkinson's disease, dementia, Alzheimer's disease or sleep apnea.

Researchers found those with the disorder were over two-and-a-half times as likely to report taking antidepressants to treat depression, with 13 percent of those with the disorder taking them compared to 6 percent of those without the disorder. People with the disorder were also two-and-a-half times as likely to have post-traumatic stress disorder. They were twice as likely to have mental illness, and over one-and-a-half times as likely to have psychological distress.

Other findings were that men were twice as likely as women to have possible REM sleep behavior disorder; 59 percent of those with the disorder were male, compared to 42 percent of those without the disorder. People with possible REM sleep behavior disorder were 25 percent more likely than those without the disorder to be moderate to heavy drinkers, with 19 percent of those with the disorder moderate to heavy drinkers compared to 14 percent of those without the disorder. They had slightly less education, an average of 13.2 years of education compared to an average of 13.6 years for those without the disorder. They also had lower income and were more likely to have smoked.

"Our research does not show that these risk factors cause REM sleep behavior disorder, it only shows they are linked," said Postuma. "Our hope is that our findings will help guide future research, especially because REM sleep behavior disorder is such a strong sign of future neurodegenerative disease. The more we understand about REM sleep behavior disorder, the better positioned we will be to eventually prevent neurologic conditions like Parkinson's disease."

A limitation of the study was that 96 percent of participants were white, 

meaning the results may not apply to people of other ethnic backgrounds.

Journal reference: Neurology 

Provided by: American Academy of Neurology 

https://medicalxpress.com/news/2018-12-factors-violent-disorder.html