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Exercise boosts brain health with chemical signals

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image: Hippocampal neurons (yellow) surrounded by astrocytes (green) in a cell culture from the study. Image provided by the authors.
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Credit: Image provided by the study authors: Taher Saif, Justin Rhodes, and Ki Yun Lee.

Physical activity is frequently cited as a means of improving physical and mental health. Researchers at the Beckman Institute for Advanced Science and Technology have shown that it may also improve brain health more directly. They studied how the chemical signals released by exercising muscles promote neuronal development in the brain.

Their work appears in the journal Neuroscience.

When muscles contract during exercise, like a bicep working to lift a heavy weight, they release a variety of compounds into the bloodstream. These compounds can travel to different parts of the body, including the brain. The researchers were particularly interested in how exercise could benefit a particular part of the brain called the hippocampus.

“The hippocampus is a crucial area for learning and memory, and therefore cognitive health,” said Ki Yun Lee, a Ph.D. student in mechanical science and engineering at the University of Illinois Urbana-Champaign and the study’s lead author. Understanding how exercise benefits the hippocampus could therefore lead to exercise-based treatments for a variety of conditions including Alzheimer’s disease.

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To isolate the chemicals released by contracting muscles and test them on hippocampal neurons, the researchers collected small muscle cell samples from mice and grew them in cell culture dishes in the lab. When the muscle cells matured, they began to contract on their own, releasing their chemical signals into the cell culture.

The research team added the culture, which now contained the chemical signals from the mature muscle cells, to another culture containing hippocampal neurons and other support cells known as astrocytes. Using several measures, including immunofluorescent and calcium imaging to track cell growth and multi-electrode arrays to record neuronal electrical activity, they examined how exposure to these chemical signals affected the hippocampal cells.

The results were striking. Exposure to the chemical signals from contracting muscle cells caused hippocampal neurons to generate larger and more frequent electrical signals — a sign of robust growth and health. Within a few days, the neurons started firing these electrical signals more synchronously, suggesting that the neurons were forming a more mature network together and mimicking the organization of neurons in the brain.

However, the researchers still had questions about how these chemical signals led to growth and development of hippocampal neurons. To uncover more of the pathway linking exercise to better brain health, they next focused on the role of astrocytes in mediating this relationship.

“Astrocytes are the first responders in the brain before the compounds from muscles reach the neurons,” Lee said. Perhaps, then, they played a role in helping neurons respond to these signals.

The researchers found that removing astrocytes from the cell cultures caused the neurons to fire even more electrical signals, suggesting that without the astrocytes, the neurons continued to grow — perhaps to a point where they might become unmanageable.

“Astrocytes play a critical role in mediating the effects of exercise,” Lee said. “By regulating neuronal activity and preventing hyperexcitability of neurons, astrocytes contribute to the balance necessary for optimal brain function.”

Understanding the chemical pathway between muscle contraction and the growth and regulation of hippocampal neurons is just the first step in understanding how exercise helps improve brain health.

“Ultimately, our research may contribute to the development of more effective exercise regimens for cognitive disorders such as Alzheimer’s disease,” Lee said.

In addition to Lee, the team also included Beckman faculty members Justin Rhodes, a professor of psychology; and Taher Saif, a professor of mechanical science and engineering.


Editor’s notes

The paper titled “Astrocyte-mediated transduction of muscle fiber contractions synchronizes hippocampal neuronal network development” can be accessed at: https://doi.org/10.1016/j.neuroscience.2023.01.028

All authors declare no conflicts of interest in this work.

Research reported in this press release was supported in part by the National Institutes of Health under award number R21 NS 109894. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Media contact: Jenna Kurtzweil, kurtzwe2@illinois.edu


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.

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Anxiety, your brain, and long Covid: What the research says

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Having anxiety and depression before a Covid infection increases the risk of developing long Covid

ISLAMABAD, (ONLINE) – Anxiety, depression, and Covid-19 can be a bad combination for your brain — and your long-term health.

Having anxiety and depression before a Covid infection increases the risk of developing long Covid, researchers have found.

Those with long Covid who develop anxiety and depression after an infection may have brain shrinkage in areas that regulate memory, emotion, and other functions as well as disruption of brain connectivity.

While many questions remain about these intertwined relationships, the associations aren’t a complete surprise. Experts already know that depression and anxiety are associated with inflammation and immune dysfunction, perhaps helping to explain the link between these mental health conditions, the risk of long Covid, and the changes in the brain.

Brain changes accompanying a Covid infection have concerned researchers since earlier in the pandemic, when U.K. Biobank researchers found brain atrophy, loss of grey matter, and decline in cognition in those infected with Covid compared with those not infected.

Common conditions

The ramifications of the research linking anxiety, depression and long Covid are far-reaching. According to the CDC, 12.5% of U.S. adults have regular feelings of anxiety (as well as nervousness and worry), and the latest Gallup Poll found that nearly 18% of adults currently have or are being treated for depression.

Managing symptoms of long Covid

WebMD’s Chief Medical Officer, John Whyte, MD, MPH, speaks with Janna Friedly, MD, MPH, a professor of physical medicine and rehabilitation at the University of Washington, about managing the symptoms of long Covid and her personal journey of recovery.

As of May 8, 10% of U.S. infected adults have long Covid, according to the CDC, and among U.S. adults ever infected, 27% have reported long Covid. Long Covid has been defined by the CDC as symptoms such as fatigue, brain fog, and cough that persist longer than 4 weeks and by the World Health Organization as symptoms persisting for 3 months or more.

Here’s a roundup of what the research shows about mental health and long Covid risk — along with other research finding that paying attention to health habits may reduce that risk.

Pre-existing depression, anxiety, and long Covid risk

A history of mental health issues — including depression, anxiety, worry, perceived stress, and loneliness — raises the risk of long Covid if infection occurs, Harvard researchers have found.

The researchers evaluated data from three large, ongoing studies including nearly 55,000 participants to determine the effects of high levels of psychological distress before a Covid infection.

“Our study was purely survey based,” said Siwen Wang, MD, the study’s lead author and a research fellow at Harvard’s T.H. Chan School of Public Health at Harvard University.

At the start of the survey in April 2020, none of the participants reported a current or previous Covid infection. They answered surveys about psychological distress at the start of the study, at 6 monthly time points, then quarterly until November 2021.

Over the follow up, 3,193 people reported a positive Covid test and 43% of those, or 1,403, developed long Covid. That number may seem high, but 38% of the 55,000 were active health care workers. On the final questionnaire, they reported whether their symptoms persisted for 4 weeks or longer and thus had long Covid by the standard CDC definition.

Wang’s team then looked at the infected participants’ psychological status. Anxiety raised the risk of long Covid by 42%, depression by 32%, worry about Covid by 37%, perceived stress, 46%, and loneliness, 32%.

Covid patients with a history of depression or anxiety are also more likely than others to report trouble with cognition in the weeks after a Covid infection and to develop brain fog and long Covid, UCLA researchers found. They evaluated 766 people with a confirmed Covid infection; 36% said their thinking was affected within 4 weeks of the infection. Those with anxiety and depression were more likely to report those difficulties.

Long Covid, then anxiety, depression, brain changes

Even mild cases of Covid infection can lead to long Covid and brain changes in those who suffer anxiety or depression after the infection, according to Clarissa Yasuda, MD, PhD, assistant professor of neurology at the University of Campinas in Sao Paulo, Brazil. She has researched long Covid’s effects on the brain, even as she is coping with being a long Covid patient.

In one of her studies, presented at the 2023 American Academy of Neurology meeting in April, she found brain changes in people with anxiety, depression, and Covid but not in those infected who did not have either mental health issue. She evaluated 254 people, median age 41, after about 82 days from their positive PCR test for Covid. Everyone completed a standard questionnaire for depression (the Beck Depression Inventory) and another for anxiety (the Beck Anxiety Inventory). She further divided them into two groups — the 102 with symptoms and the 152 who had no symptoms of either depression or anxiety.

Brain scans showed those with Covid who also had anxiety and depression had shrinkage in the limbic area of the brain (which helps process emotion and memory), while those infected who didn’t have anxiety or depression did not. The researchers then scanned the brains of 148 healthy people without Covid and found no shrinkage.

The atrophy, Yasuda said, “is not something you can see with your eyes. It was only detected with computer analysis. Visualization on an MRI is normal.”

The number of people in this study with mental health issues was surprisingly high, Yasuda said. “It was intriguing for us that we noticed many individuals have both symptoms, anxiety and depression. We were not expecting it at that proportion.”

The researchers found a pattern of change not only in brain structure but in brain communication. They found those changes by using specialized software to analyze brain networks in some of the participants. Those with anxiety and depression had widespread functional changes in each of 12 networks tested. The participants without mental health symptoms showed changes in just 5 networks. These changes are enough to lead to problems with thinking skills and memory, Yasuda said.

Explaining the links

Several ideas have been proposed to explain the link between psychological distress and long Covid risk, Wang said. “The first and most mainstream mechanism for long Covid is chronic inflammation and immune dysregulation,” she said. “Several mental health conditions, such as anxiety and depression, are associated with inflammation and dysfunction and that might be the link between depression, anxiety, and long Covid.”

Another less mainstream hypothesis, she said, is that “those with long Covid have more autoantibodies and they are more likely to have blood clotting issues. These have also been found in people with anxiety, depression, or other psychological distress.”

Other researchers are looking more broadly at how Covid infections affect the brain. When German researchers evaluated the brain and other body parts of 20 patients who died from non-Covid causes but had documented Covid infections, they found that 12 had accumulations of the SARS-CoV-2 spike protein in the brain tissue as well as the skull and meninges, the membranes that line the skull and spinal cord. Healthy controls did not.

The findings suggest the persistence of the spike protein may contribute to the long-term neurological symptoms of long Covid and may also lead to understanding of the molecular mechanisms as well as therapies for long Covid, the researchers said in their preprint report, which has not yet been peer-reviewed.

 

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New treatment shows promise for some women with cervical cancer

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IANS

Toronto, June 4

A simple hysterectomy, a surgical procedure where the uterus and cervix is removed, is a safe treatment option that can improve quality of life for women with early-stage, low-risk cervical cancer, according to results from the phase III clinical trial.

The study states that a simple hysterectomy resulted in similar outcomes in terms of keeping them cancer-free, compared to the standard radical hysterectomy, which removes the uterus, cervix, upper parts of the vagina and other nearby tissues.

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Because radical hysterectomy is a more complex surgery, it is associated with more acute and long-term side effects, as well as potential impacts on quality of life and sexual health for patients.

“Sexual health and quality of life are very important considerations for patients undergoing cancer treatment,” said Dr. Lori Brotto, a professor of obstetrics and gynaecology at University of British Columbia.

“The findings from this study indicate that patients can expect fewer negative effects on sexual health and many other facets of quality of life with simple hysterectomy while not compromising effects on recurrence and survival rates,” Brotto added.

The study looked at the three-year pelvic recurrence rate and other health outcomes in 700 patients from 12 countries receiving both simple and radical hysterectomies.

The findings, presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that the extra-pelvic recurrence-free survival, the relapse-free survival, and the overall survival were comparable between the two groups.

There were fewer intraoperative urological surgical complications and fewer immediate and long-term bladder problems in the simple hysterectomy group.

Several quality-of-life aspects, such as body image, pain, and sexual health, were consistently more favourable in them.

“These results are important because it demonstrates, for the first time, that a simple hysterectomy is a safe option for women with carefully selected early-stage low-risk cervical cancer,” said Dr. Marie Plante, the study lead and a gynecologic oncologist at Universite Laval in Quebec.

“This trial will likely be practice-changing, with the new standard-of-care treatment for patients with low-risk disease being a simple hysterectomy instead of radical hysterectomy.” Worldwide, cervical cancer is the fourth most diagnosed cancer and fourth most common cause of cancer death in women.

About 44 per cent of women with cervical cancer are diagnosed with early-stage disease, of which a significant proportion will meet low-risk criteria, according to the team.

When detected at an early stage, the 5-year relative survival rate for invasive cervical cancer is 92 per cent.

#Canada
#Cancer
#Toronto

 

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AstraZeneca’s Tagrisso slashes death risk in certain post-surgery lung cancer patients

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By Natalie Grover

LONDON (Reuters) – AstraZeneca’s lung cancer therapy, Tagrisso, cut the risk of death by more than half in patients with a certain form of lung cancer who were diagnosed early enough to have their tumour surgically removed, trial data showed.

Tagrisso is already the crown jewel in the Anglo-Swedish drugmaker’s portfolio, raking in $5.4 billion last year.

The drug has regulatory approvals across multiple geographies for certain patients with so-called non small cell lung cancer (NSCLC) who have a mutation of the EGFR gene.

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The latest data, presented at the American Society of Clinical Oncology (ASCO) meeting, establishes Tagrisso as the backbone treatment for EGFR-mutated lung cancer, said Susan Galbraith, executive VP of oncology R&D at AstraZeneca in a statement.

In a 682-patient trial called ADAURA, Tagrisso was evaluated against a placebo in earlier-stage EGFR-mutated NSCLC patients who had undergone surgery to remove their primary tumour.

The majority of such patients eventually see their cancer return despite surgery and add-on chemotherapy.

In the trial, Tagrisso or a placebo was given to patients to assess whether the AstraZeneca therapy could keep their cancer at bay.

Data showed Tagrisso slashed the risk of death by 51% compared to placebo.

“This is a pretty dramatic and remarkable improvement,” said Dave Fredrickson, executive vice president of oncology at AstraZeneca in an interview with Reuters.

An estimated 88% of patients treated with Tagrisso were alive at five years compared to 78% on placebo, trial data also showed.

Outside of chemotherapy, there are no drugs apart from Tagrisso that have shown to help patients with EGFR-mutated lung cancer live longer, Fredrickson highlighted, adding that there are probably a third of eligible patients who are not yet being prescribed Tagrisso.

“We would hope that we would be able to use these data to be able to close that gap,” he said.

AstraZeneca is also expecting to provide details on the impact of combining Tagrisso with chemotherapy in patients with advanced EGFR-mutated lung cancer later this year.

(Reporting by Natalie Grover in London; Editing by Angus MacSwan)

 

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