Day: June 2, 2023

Categories : Immune System Neurodegenerative DiseasesTags : Leave a comment

Scientists Strengthen Evidence Linking Autoimmunity and Schizophrenia

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Links have been reported between schizophrenia and autoimmunity. In a study published in Brain Behavior and Immunity, Japanese researchers identified autoantibodies that target a ‘synaptic adhesion protein’, neurexin 1α, in a subset of patients with schizophrenia. When injected into mice, the autoantibodies caused many schizophrenia-related changes.

What is a synaptic protein, and why might it be linked to schizophrenia? Synaptic adhesion proteins are specialised proteins that bind to create physical connections between brain cells. These connections, called synapses, allow the cells to communicate by passing molecules back and forth. Both synapses and autoimmunity are known to be associated with schizophrenia, so the research team from Tokyo Medical and Dental University (TMDU) decided to investigate autoantibodies that target synaptic proteins in patients with schizophrenia.

“In around 2% of our patient population, we identified autoantibodies against the synaptic protein neurexin 1α, which is expressed by one cell in the synapse and binds to proteins known as neuroligins on the other cell in the synapse,” says lead author of the study Hiroki Shiwaku. “Once we had identified these autoantibodies, we wanted to see if they were able to cause schizophrenia-related changes.”

To do this, the researchers isolated autoantibodies from some of the patients with schizophrenia and injected them into the cerebrospinal fluid of mice, so that the autoantibodies would travel into the brain. In these mice, the autoantibodies blocked neurexin 1α and neuroligin binding and altered some related synaptic properties. The administration of these autoantibodies also resulted in fewer synapses in the brains of mice and schizophrenia-related behaviours, such as reduced social behaviour toward unfamiliar mice and reduced cognitive function.

“Together, our results strongly suggest that autoantibodies against neurexin 1α can cause schizophrenia-related changes, at least in mice,” explains Hiroki Shiwaku. “These autoantibodies may therefore represent a therapeutic target for a subset of patients with schizophrenia.”

Schizophrenia has a wide variety of both symptoms and treatment responses, and many patients have symptoms that are resistant to currently available treatment options. Therefore, the identification of possible disease-causing autoantibodies is important for improving symptom control in patients with schizophrenia. It is hoped that the results of this investigation will allow patients with autoantibodies that target neurexin 1α – all of whom were resistant to antipsychotic treatment in the present study — to better control their symptoms in the future.

Source: Tokyo Medical and Dental University

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The Geometry of the Brain May Influence Brain Functions

On By ModernMedia
Photo by Robina Weermeijer on Unsplash

For over 100 years, scientists have thought that the brain activity patterns that define human consciousness arose from how different brain regions communicate with each other through trillions of cellular connections.

Now, by examining more than 10 000 different maps of human brain activity, Monash University-led researchers found that the overall shape of a person’s brain has a much greater influence on thought and behaviour than its neuronal connectivity. This may sound like the old pseudoscience of phrenology, which based theories of personality and cognition on the shape of the head and its bumps.

Not so for this study, which combines approaches from physics, neuroscience and psychology to overturn the century-old model revolving around complex brain connectivity, instead revealing a relationship between brain shape and activity. The researchers published their ground-breaking findings in the journal Nature.

Lead author Dr James Pang said the findings were significant because they greatly simplified the way that we can study how the brain functions, develops and ages.

“The work opens opportunities to understand the effects of diseases like dementia and stroke by considering models of brain shape, which are far easier to deal with than models of the brain’s full array of connections,” Dr Pang said.

“We have long thought that specific thoughts or sensations elicit activity in specific parts of the brain, but this study reveals that structured patterns of activity are excited across nearly the entire brain, just like the way in which a musical note arises from vibrations occurring along the entire length of a violin string, and not just an isolated segment,” he said.

Using magnetic resonance imaging (MRI), the researchers studied eigenmodes, which are the natural patterns of vibration or excitation in a system, where different parts of the system are all excited at the same frequency. Eigenmodes are normally used in areas such as physics to study physical systems only recently have they been applied to studying brain.

Their study focused on developing the optimal way to construct the eigenmodes of the brain.

“Just as the resonant frequencies of a violin string are determined by its length, density and tension, the eigenmodes of the brain are determined by its structural – physical, geometric and anatomical – properties, but which specific properties are most important has remained a mystery,” said co-lead author, Dr Kevin Aquino, of BrainKey and The University of Sydney.

‘Like the shape of a drum influences the sounds that it can make’

The team, led by Professor Alex Fornito, compared how well eigenmodes derived from models of brain shape could account for different patterns of activity as opposed to eigenmodes from models of brain connectivity.

“We found that eigenmodes defined by brain geometry – its contours and curvature – represented the strongest anatomical constraint on brain function, much like the shape of a drum influences the sounds that it can make,” said Fornito.

“Using mathematical models, we confirmed theoretical predictions that the close link between geometry and function is driven by wave-like activity propagating throughout the brain, just as the shape of a pond influences the wave ripples that are formed by a falling pebble,” he said.

“These findings raise the possibility of predicting the function of the brain directly from its shape, opening new avenues for exploring how the brain contributes to individual differences in behavior and risk for psychiatric and neurological diseases.”

The research team found that, across over 10 000 MRI activity maps, obtained as people performed different tasks developed by neuroscientists to probe the human brain, activity was dominated by eigenmodes with spatial patterns that have very long wavelengths, extending over distances exceeding 40 mm.

“This result counters conventional wisdom, in which activity during different tasks is often assumed to occur in focal, isolated areas of elevated activity, and tells us that traditional approaches to brain mapping may only show the tip of the iceberg when it comes to understanding how the brain works,” Dr Pang said.

Source: MedicalXpress

Categories : Diet and Nutrition GastrointestinalTags : Leave a comment

Scientists Find that The Sweetener Sucralose Breaks up DNA

On By ModernMedia
Photo by Sharon Mccutcheon on Unsplash

A new study published in the Journal of Toxicology and Environmental Health, Part B, found that a chemical formed during the digestion of widely used sweetener is “genotoxic,” meaning it breaks up DNA. The chemical is also found in trace amounts in the sweetener itself, and the finding raises questions about how the sweetener may contribute to health problems.

At issue is sucralose, a widely used artificial sweetener. Previous work by the same research team established that several fat-soluble compounds are produced in the gut after sucralose ingestion. One of these compounds is sucralose-6-acetate.

“Our new work establishes that sucralose-6-acetate is genotoxic,” says Susan Schiffman, corresponding author of the study and an adjunct professor at North Carolina State University. “We also found that trace amounts of sucralose-6-acetate can be found in off-the-shelf sucralose, even before it is consumed and metabolised.

“To put this in context, the European Food Safety Authority has a threshold of toxicological concern for all genotoxic substances of 0.15 micrograms per person per day,” Schiffman says. “Our work suggests that the trace amounts of sucralose-6-acetate in a single, daily sucralose-sweetened drink exceed that threshold. And that’s not even accounting for the amount of sucralose-6-acetate produced as metabolites after people consume sucralose.”

For the study, researchers conducted a series of in vitro experiments exposing human blood cells to sucralose-6-acetate and monitoring for markers of genotoxicity.

“In short, we found that sucralose-6-acetate is genotoxic, and that it effectively broke up DNA in cells that were exposed to the chemical,” Schiffman says.

The researchers also conducted in vitro tests that exposed human gut tissues to sucralose-6-acetate.

“Other studies have found that sucralose can adversely affect gut health, so we wanted to see what might be happening there,” Schiffman says. “When we exposed sucralose and sucralose-6-acetate to gut epithelial tissues – the tissue that lines your gut wall – we found that both chemicals cause ‘leaky gut.’ Basically, they make the wall of the gut more permeable. The chemicals damage the ‘tight junctions,’ or interfaces, where cells in the gut wall connect to each other.

“A leaky gut is problematic, because it means that things that would normally be flushed out of the body in feces are instead leaking out of the gut and being absorbed into the bloodstream.”

The researchers also looked at the genetic activity of the gut cells to see how they responded to the presence of sucralose-6-acetate.

“We found that gut cells exposed to sucralose-6-acetate had increased activity in genes related to oxidative stress, inflammation and carcinogenicity,” Schiffman says.

“This work raises a host of concerns about the potential health effects associated with sucralose and its metabolites. It’s time to revisit the safety and regulatory status of sucralose, because the evidence is mounting that it carries significant risks. If nothing else, I encourage people to avoid products containing sucralose. It’s something you should not be eating.”

Source: NC State University

Categories : COVID General InterestTags : Leave a comment

New Podcast Series Reflects on Childhood in South Africa Through and Beyond COVID-19

On By ModernMedia
Photo by Hush Naidoo Jade Photography on Unsplash

The ‘Phezulu: Looking Up’ podcast series launched today by UNICEF South Africa (https://www.UNICEF.org/SouthAfrica/) tells the stories of the impact of the COVID-19 years on children and young people and how, with the right support and opportunities, children and young people are determined to build a safer, fairer and better post pandemic South Africa.  

The eight-part series delves into issues such as mental wellbeing, disrupted education and access to child healthcare; including routine childhood immunisations, through the voices of children and young people and experts working to mitigate the impact.

“Children and adolescents were affected by every aspect of the COVID-19 pandemic and this podcast series tells their stories of resilience,” said Muriel Mafico, UNICEF South Africa Deputy Representative. “Importantly, the episodes also reflect on the response to share learnings, including how the roll-out of the COVID-19 vaccine saved countless lives and re-opened our world,”

The podcast series features expert analysis and voices, including contributions from academics, all of whom continue to play a critical role in the ongoing recovery for every child. The series not only highlights the indirect impact of COVID-19 on children and youth, but also how COVID-19 vaccinations changed the trajectory of the crisis by enabling children and adolescents to resume their childhoods.

The series will be available on a weekly basis, on all major podcast platforms from 23rd May 2023. Listeners can now subscribe and join the conversation. This production was made possible thanks to the generous support of the German Federal Foreign Office and other partners.

For more information, please see the following links:
https://www.UNICEF.org/southafrica/
https://apo-opa.info/42dIxHD

Categories : Metabolic Disorders PaediatricsTags : Leave a comment

Cholesterol may Explain The Link Between Childhood Obesity and Early Puberty

On By ModernMedia
Photo by Patrick Fore on Unsplash

As childhood obesity increases the world, children are entering puberty earlier and earlier – particularly girls. According to a survey, the onset of puberty occurs on average three months earlier for girls in every decade since 1977. Early, or precocious, puberty can leave children with psychological and social problems, as well leading to shorter adult heights. Studies also suggest that early puberty can increase the risk of developing cancer, diabetes, depression and cardiovascular disease later on in life.

While a scientific explanation has been lacking, the link between childhood obesity and early puberty has long been apparent. The more body fat a child has, the greater their likelihood of beginning puberty at an earlier age. Now, researchers have found what may be part of the answer in Drosphila fruit flies, publishing their results in Current Biology.

“Cholesterol is a fat. So, if you’re overweight, your body fat harbours more cholesterol. And it turns out that higher cholesterol is a key to earlier maturation in the fruit fly, our model organism. Our results demonstrate that the amount of cholesterol in adipose tissue and in certain support cells in the brain affects the growth of fruit flies and controls when they reach maturity,” explains Professor Kim Rewitz, a lead author of the study.

He adds, “And because the systems in fruit flies and humans are remarkably similar, we believe that the same may apply to humans – ie, that cholesterol in adipose tissue may help explain the connection between childhood obesity and early puberty.”

Puberty at ‘critical weight’

Professor Rewitz and the University of Copenhagen’s Department of Biology research team tested their hypothesis by putting fruit fly larvae on a “fatty diet” of cholesterol-packed foods. The development of these larvae was compared with larvae on a normal diet.

“We observed that larvae on the cholesterol diet consistently grew faster and entered ‘puberty’ sooner. It turned out that the increase of cholesterol stored in the fruit flies’ body fat and support cells in the brain increases the release of growth hormones that cause the animals to grow faster. Growth and size is a signal to the body for when to trigger puberty,” says Kim Rewitz. 

The professor explains that in fruit flies, the signal to undergo maturation is when their weight and amount of body fat reach a certain point during development:

“In one way or another, animals need to know when they’re large enough to reach sexual maturity and be able to reproduce. Organisms have a checkpoint in their development that they must pass to enter puberty known as ‘Critical Weight’. This checkpoint is found in fruit flies and most likely in humans too. This means that both fruit fly larvae and children probably need to reach a certain body size and have a certain amount of fat stored to enter puberty. What we’ve found is that the amount of cholesterol stored in body fat plays an important role in this process.

“We see that fruit flies have a mechanism that senses how much cholesterol is stored in their body fat and support cells in the brain. At a certain point, the system then sends a signal to the brain centres that triggers maturation by producing steroid hormones. In humans, these correspond to testosterone and oestrogen.”

However, it also means that if the amount of stored cholesterol increases, the organism can actually fail to estimate its overall size accurately, so that it hits the critical weight checkpoint earlier than it normally would:

“Because overweight children have more body fat, they will probably also have stored more cholesterol at an earlier point in their development. So, if our assumption that the same mechanism exists in humans holds true, it could help to explain early puberty in obese children,” says the researcher.

Cholesterol may influence cancer as well

Professor Rewitz concludes that with part of the puzzle in hand, scientists can search for more clues and treatment. In the meantime, lifestyle changes remain the best solution for childhood obesity.

Professor Rewitz and his research colleagues have now started to look deeper into the significance of the cholesterol mechanism for cancer development. Their research also shows that, via the same mechanism, cholesterol can activate cell growth that leads to cancer.

Source: University of Copenhagen