Tag: 8/7/26

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Researchers Affirm Long-held Belief that Viruses Can Trigger Parkinson’s Disease

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A new study shows that a common virus can induce Parkinson’s-like brain damage and movement problems

Source: CC0

Scientists usually use animal models when studying Parkinson’s disease because these models mimic the disease well. They are limited, however, because they require either gene modifications or the injection of toxicants, which may not accurately represent how the disease occurs in humans.

But now, researchers at Texas A&M University have developed a model that uses a nontoxic way to generate the symptoms of Parkinson’s: infection with a virus called Theiler’s murine encephalomyelitis virus (TMEV), a natural pathogen in mice.

Their study is a game changer because it proves that a simple viral infection can trigger the exact brain damage and physical disabilities in animal models that are seen in people with Parkinson’s disease – and it sets the stage for additional studies.

“The toxic-exposure models are useful for studying Parkinson’s, but not all people who are exposed to chemicals go on to develop Parkinson’s, so these models cannot show all the ways a disease as complex as Parkinson’s actually begins or develops over time in people,” said Candice Brinkmeyer-Langford, a neurogenerative disease expert with the Texas A&M University School of Public Health at Texas A&M Health.

Parkinson’s affects more than 10 million people worldwide, making it second only to dementia among brain disorders. It destroys the cells that produce dopamine, a chemical essential for smooth body movement, leading to problems with balance and walking, tremors in the hands or fingers and overall stiffness, as well as mental or emotional distress.

Its origins are unknown, but for decades, experts have believed that the disease could be triggered by the brain inflammation caused by viruses – even those contracted decades earlier – as well as by a combination of a person’s genetics and environmental factors. This idea recently was affirmed by Brinkmeyer-Langford and others at Texas A&M in the case of another devastating motor neuron disease, amyotrophic lateral sclerosis (ALS).

“Viruses are known to cause entirely different diseases based on a person’s genetics,” she said. “For example, the Epstein-Barr virus causes mononucleosis, but may also contribute to cancer or multiple sclerosis, and SARS-CoV-2 can attack the heart and brain as well as the lungs.”

For this pilot study to test the validity of TMEV in studying Parkinson’s, the researchers conducted experiments to measure the following:

  • Brain cell infection and damage. One week after infection, the researchers confirmed that the virus had infected the dopamine-producing brain cells. At one month after infection, the dopamine-producing cells were destroyed in the site of viral infection. Dopamine-induced behaviours were compared between 13 infected animal models and 14 healthy control animal models after administering a dopamine-mimicking drug which produced a distinct movement pattern confirming dopamine neuron loss. This test confirmed that the virus caused a significant loss of these crucial dopamine brain cells over time.
  • Speed and coordination. They compared 13 infected animal models against 14 healthy control animal models to track and measure their motor skills with a standard assessment called the pole test to determine if losing dopamine-producing cells causes the physical movement problems typically seen in Parkinson’s patients. Animal models infected with TMEV had slower times to complete the test compared to the healthy control models, and this still was the case at week 20, when the study ended.
  • Gait abnormalities. They used a specialised treadmill, which evaluated over 100 factors involved in walking, motor function and balance, to analyse how quickly and efficiently the animal models walked. The test confirmed that the virus caused physical weakness following the loss of dopamine producing cells due to viral infection, proving that the virus damaged the brain in a similar way as seen in Parkinson’s patients.

Now that this innovative model has been proven, Brinkmeyer-Langford said future studies will include testing the TMEV model directly against standard, older animal models used in Parkinson’s research, looking for early warning signs and biological markers for Parkinson’s and analyzing how the body’s immune response to a virus changes the brain.

“The clock is ticking, since the rapidly aging global population means the number of people with Parkinson’s is expected to jump significantly,” she said.

By Ann Kellett

Source: Texas A&M University

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A Sleepless Night Increases Synaptic Connections

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An increase in a marker for connections was associated with deeper sleep during later naps

Photo by Andrea Piacquadio

A night without sleep produced increased markers of connections between brain cells, showing that sleep in humans may be important for restoring cellular balance in the brain, according to a study published June 23rd in the open access journal PLOS Biology by David Elmenhorst from the Forschungszentrum Jülich Institute of Neuroscience and Medicine in North Rhine-Westphalia, Germany, and colleagues.

Scientists have long wondered why exactly humans and other animals need to sleep. One potential mechanism is that sleep is required to restore synaptic connections and homeostasis in the brain. Synapses – the connections between brain cells – become stronger during wakefulness. This increases the amount of energy the brain needs and leads to buildup of proteins in the brain. Sleep is thought to reset these levels, reducing synaptic connections and restoring homeostasis, but evidence has thus far been limited to animal models. To determine whether the synaptic homeostasis hypothesis is supported in humans, the authors of this study used positron emission tomography (PET) to look for markers of synaptic vesicle glycoprotein 2A (SV2A), a marker of brain synapses in 40 participants, half of whom had gone one night without sleep.

The authors found that after 28 hours of continuous wakefulness, the sleep deprivation group had higher measures of SV2A in several brain regions, including the hippocampus (an area important for memory), and the thalamus, an important information relay in the brain. When the sleep-deprived participants were allowed a two-hour nap, higher levels of SV2A were associated with more slow wave activity during sleep, a marker of deep sleep and sleep pressure. While SV2A is only a proxy for brain cell connections and the elevations were relatively small, the results support the synaptic homeostasis model of sleep, and suggest a biological connection between the need for sleep and the buildup of cell connections. 

The authors add, “During sleep deprivation, the brain remains awake longer and continues to process stimuli and information. Our study shows that after approximately 28.5 hours of wakefulness, a marker for synaptic density increases in several brain regions. This suggests that sleep deprivation not only causes fatigue but is also accompanied by measurable changes in neural connections.”

Provided by PLOS

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Higher Vitamin A Levels Linked to Better Lung Function in Asthmatic Kids and Adults

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Vitamin D shows similar benefits in adults with asthma, including slower biological ageing

Photo by cottonbro studio from Pexels

Higher levels of circulating vitamin A are linked to better lung function in children and adults with asthma, while vitamin D shows similar benefits in adults, including slower biological ageing, finds the first study of its kind, published online in the respiratory journal Thorax.

Poor lung function is a key predictor of death, irrespective of whether or not a person has lung disease. And making sure that the lungs keep working well is essential for staving off long term respiratory conditions, explain the researchers.

Previously published research suggests that vitamins A and D both protect against and worsen asthma, as well as influencing lung development, depending on the dose and context, they add.

To clarify the role of these vitamins, the researchers drew on two groups of participants with asthma: 1165 children in the GACRS (Genetic Epidemiology of Asthma in Costa Rica Study); and 1041 adults in the ODOLLFA (Omic Determinants of Longitudinal Lung Function in Asthma).

Small molecules that fine-tune the activity of genes (serum microRNAs or miRNAs for short) and those that mark genes as either active or inactive (DNA methylation), plus levels of vitamins A and D, were measured in all the participants.

Lung capacity/health was assessed through measures of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and the FEV:FVC ratio.

In adults, further analysis assessed whether methylation status and miRNAs influenced the association between the vitamins and lung function or epigenetic ageing – the response of genes to external biological and environmental factors which then promotes cellular ageing.

The findings showed that children and adults with asthma and higher vitamin A levels had better lung function (FEV1 and FVC) than those with lower levels.

And among adults with asthma, those with higher vitamin D levels of at least 30 ng/ml had better lung function than those with lower levels. They also had less evidence of epigenetic ageing, suggesting that vitamin D may help slow biological ageing, particularly in people with asthma, say the researchers.

“These findings emphasise the value of adequate vitamin D, not only for lung health but also in slowing age-related processes,” they write.

In people with asthma, vitamin D deficiency is more common and is associated with more severe disease, worse asthma control, higher inhaled steroid need and more frequent  sudden worsening of asthma symptoms, they explain.

The researchers identified MiRNAs that regulate 248 genes commonly associated with vitamins A and D in both age groups, which, further analysis suggests, are involved in controlling inflammation and lung function.

This secondary analysis also revealed that changes in the expression of specific miRNAs strongly influence the effects of vitamins A and vitamin D on lung function and epigenetic ageing.

“To our knowledge, this is the first study to integrate vitamin A and D levels with lung function and epigenetic markers – miRNA expression and DNA methylation – in both children and adults with asthma,” write the researchers.

Lung function was inversely correlated with all age acceleration measures, reinforcing the link between respiratory health and ageing,” they add.

They conclude: “Our findings emphasise that epigenetic mechanisms play a key role in mediating the effects of vitamins on lung function in individuals with asthma, pointing to potential targets for personalised nutrition and therapeutic strategies in asthma care.”

In a linked editorial, Drs Sze Man Tse and Genevieve Mailhot of the CHU Sainte-Justine Research Center, Montreal, and the University of Montreal, caution: “While these findings open a novel line of investigation linking vitamin D, biological ageing and lung health, there is a need for further studies to clarify causality.”

But they add: “By examining the underlying biological mechanisms, [the researchers have] revealed a nuanced interplay between vitamins A and D, lung function, and their epigenetic mediators.

“Their findings highlight age-dependent and age-independent mechanisms, underscoring complex interactions between vitamin levels and lung physiology.”

And they conclude: “Overall, advancing our understanding of how nutritional exposures impact gene regulation may open new avenues for managing asthma across the lifespan.”

Source: The BMJ Group

Categories : EndocrinologyTags : Leave a comment

Cortisol from Adrenal Tumours Progressively Raises Cardiovascular Risk

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Landmark international study finds persistent mild cortisol excess drives hypertension progression, challenging the standard diagnostic test.

A graphic of a human skeleton, also showing the kidneys with the adrenal glands on top, highlighted in red.
The adrenal glands produce the steroid hormone cortisol, a master regulator of metabolism, blood pressure and immune function.

A major new study, led by the University of Birmingham and published in The Lancet Diabetes & Endocrinology, has shown that cortisol levels in patients with adrenal tumours are far less stable than previously assumed.

The study also identified that those in whom cortisol remains persistently elevated carry a significantly greater risk of worsening high blood pressure and a heavier overall cardiometabolic burden.

Cortisol, often referred to as the “stress hormone”, is a steroid hormone produced by the adrenal glands that acts as a master regulator of metabolism, blood pressure, and immune function. When benign tumours form on the adrenal glands (found incidentally in 3-7% of adults) they can cause the body to produce cortisol independently of normal regulatory controls, a condition known as mild autonomous cortisol secretion (MACS). Until now, it was unclear how cortisol levels in these patients change over time, and what that means for their long-term health.

The study of over 2500 patients is the largest study of its kind to examine how cortisol patterns evolve over time in patients with benign adrenal tumours and what this means for cardiovascular outcomes.

These findings should prompt us to think more carefully about which patients need closer follow-up, and whether active treatment to reduce cortisol excess – including surgery in selected cases – could protect their long-term cardiovascular health.

Alessandro Prete, Clinical Associate Professor in Endocrinology and Diabetes

The study followed 2525 patients with benign adrenal tumours for an average of nearly 7 years. Each patient underwent repeated hormonal testing using the 1mg overnight dexamethasone suppression test, the standard clinical test used to assess whether the adrenal gland is overproducing cortisol autonomously. Patients were classified based on whether their cortisol levels remained normal, remained elevated (persistent MACS), or changed between categories over time.

The researchers found that cortisol secretion status changed in 22% of patients, far more frequently than previously recognised, with most changes occurring within the first three years after diagnosis. These findings challenge the assumption that a single hormonal test is sufficient to characterise a patient’s long-term cortisol profile.

Patients with persistent MACS had the greatest overall cardiovascular burden and faced a 34% higher rate of worsening high blood pressure than those with persistently normal cortisol. Over 10 years, patients with persistent MACS lost an average of 2 years of well-controlled hypertension-free time compared with those whose cortisol remained normal – a clinically meaningful difference in long-term blood pressure control.

Cardiometabolic burden refers to the combined impact of interrelated metabolic and cardiovascular risk factors (including obesity, high blood pressure, type 2 diabetes, and high cholesterol) on overall health, predisposing serious, chronic diseases such as heart failure, heart attack, and stroke.

The study identified patients with persistently abnormal cortisol levels (persistent MACS) as a clinically important, higher-risk group who may benefit from closer monitoring and more proactive management of modifiable risk factors – including blood pressure, cholesterol, weight, and smoking. The results are also consistent with recent randomised trial data, also published in The Lancet Diabetes & Endocrinology, showing that surgery to remove the adrenal tumour can improve blood pressure control in MACS.

Professor Alessandro Prete, Clinical Associate Professor of Endocrinology in the Department of Metabolism and Systems Science at the University of Birmingham, Co-lead for the National Institute for Health and Care Research (NIHR) Biomedical Research Centre: Birmingham’s Women’s Metabolic Health theme, through which the study was delivered, and corresponding author and senior investigator of the study, said: “For many years, the assumption has been that a single hormone test at adrenal tumour diagnosis tells us everything we need to know about a patient’s cortisol status.

“This study shows that it is simply not the case – cortisol levels change over time in a substantial proportion of patients, and those in whom they remain persistently elevated are at a meaningfully higher risk of developing uncontrolled blood pressure.”

The study also provides important new evidence to inform the ongoing debate around whether, and how often, cortisol testing should be repeated in patients with benign adrenal tumours. Current guidelines recommend repeating the test only in specific clinical circumstances; the authors of the study are calling for prospective studies to determine whether repeated hormonal assessment contributes meaningfully to risk stratification beyond established cardiovascular risk factors. 

Source: University of Birmingham

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Uncovering Sex-specific Immune Differences in Glioblastoma

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Photo by Anna Shvets

Men and women experience many diseases very differently. Certain diseases present more commonly in one sex than in another. Some conditions like heart attacks may cause different symptoms in men and women. Some treatments work better or not at all for one sex over the other.

Cancer is no exception. There are major differences in male and female immune systems, a system critical for cancer’s growth and for successfully becoming cancer-free. For example, some immunotherapies work better in men than in women and vice versa.

Glioblastoma, the most common and fatal form of brain cancer, is more common and more deadly in men than in women. The reasons behind this difference and how the cancer’s biology differs between men and women remain largely unclear.

Now, a study has identified a cellular mechanism that differs between male and female laboratory models with glioblastoma. The study was published in the journal Nature Cancer and led by Defne Bayik, PhD, assistant professor of molecular and cellular pharmacology at the University of Miami Miller School of Medicine, and Asmita Pathak, PhD, a former postdoctoral fellow in the Bayik Lab.

“We have a growing appreciation that cancer doesn’t act the same way in men and women. There are differences in incidence rates. There are differences in treatment responses. There are differences in outcomes,” Dr Bayik said. “But we don’t really have a good, fundamental understanding of the mechanisms underlying these observational studies.”

Delving Into Immune Differences

To uncover that mechanism for glioblastoma, Dr Bayik and her colleagues focused on a certain class of immune cells in the brain known as myeloid-derived suppressor cells, or MDSCs. As their name suggests, these cells suppress other cells’ immune activity, especially that of T cells. In healthy contexts, their activity is important for regulating the immune system and keeping inflammation under control. But in the context of cancer, these cells are often recruited by tumours to suppress surrounding T cells and other immune cells, protecting cancerous cells from the rest of the immune system and allowing them to grow unchecked.

In previous work, Dr Bayik found sex-specific differences in the immune landscape of glioblastoma, with higher levels of monocytic myeloid-derived suppressor cells associated with disease in male laboratory models. Granulocytic MDSCs play a more prominent role in females. In studies of human glioblastoma tumours, she observed a similar pattern. Men tend to have more monocytic MDSCs within their tumours, Granulocytic MDSCs, or proteins associated with these cells, correlate with worse outcomes for women but not for men.

Women still constitute 40% of glioblastoma patients. By identifying these differences, we can better tailor treatments for both men and women.

Dr Defne Bayik

In the new study, Dr Bayik and her colleagues wanted to understand what drives this difference. How do granulocytic MDSCs act to promote cancer growth in female but not male laboratory models? In Dr Bayik’s previous study, she’d found several drug candidates that are predicted to act on granulocytic MDSCs. A few of these candidate drugs target proteins related to GABA, a brain signaling molecule also known as a neurotransmitter.

By exposing different populations of MDSCs to GABA in the lab, the scientists found that the neurotransmitter specifically affects cellular metabolism only in female granulocytic MDSCs. The process is unaffected in male MDSCs. They also found that this reprogramming of the cells’ metabolism by GABA made the granulocytic MDSCs more immunosuppressive. Finally, they found that blocking the GABA receptor in female laboratory models with glioblastoma improved their outcome. This had no effect on male laboratory models with the cancer.

Potential for treatment personalised by sex

Dr Bayik and her colleagues found that many of their lab findings held up in human samples donated by patients with glioblastoma. Tumour biopsies from women had higher levels of GABA and the GABA receptor in granulocytic MDSCs than did those from men. They also found that GABA reprograms granulocytic MDSC metabolism in women as it does in lab models.

These findings point to the potential for a sex-specific treatment for glioblastoma, Dr. Bayik said. She’s currently working to understand the basis for the difference in cellular metabolism in these immune cells between male and female laboratory models. Further uncovering the mechanism of this sex difference will help her and other scientists find new potential drug targets for the disease. MDSCs are involved in many other types of cance. Drugs that target these cells could have broader applications than just glioblastoma.

“Glioblastoma may be more common in men, but women still constitute 40% of patients,” said Dr Bayik. “By identifying these differences, we can better tailor treatments for both men and women.”

By Rachel Tompa, PhD

Source: University of Miami