Do You Have a Saggy Brain?

Credit: Newcastle University
New research from Newcastle University, UK, in collaboration with the Federal University of Rio de Janeiro, investigated the way the human brain folds and how this ‘cortical folding’ changes with age. Losing the youthful firmness and elasticity in our skin is one of the first outward signs of ageing. Now it seems it’s not just our skin that starts to sag - but our brains too.

Linking the change in brain folding to the tension on the cerebral cortex - the outer layer of neural tissue in our brains - the team found that as we age, the tension on the cortex appears to decrease. This effect was more pronounced in individuals with Alzheimer’s disease.

Publishing their findings today in the academic journal PNAS, the team say this new research sheds light on the underlying mechanisms which affect brain folding and could be used in the future to help diagnose brain diseases.

Lead author Dr Yujiang Wang (pictured) of Newcastle University, explains: “One of the key features of a mammalian brain is the grooves and folds all over the surface – a bit like a walnut - but until now no-one has been able to measure this folding in a consistent way.

“By mapping the brain folding of over 1,000 people, we have shown that our brains fold according to a simple universal law. We also show that a parameter of the law, which is interpreted as the tension on the inside of the cortex, decreases with age.

“In Alzheimer’s disease, this effect is observed at an earlier age and is more pronounced. The next step will be to see if there is a way to use the changes in folding as an early indicator of disease.”

Common in all mammals

The expansion of the cerebral cortex is the most obvious feature of mammalian brain evolution and is generally accompanied by increasing degrees of folding of the cortical surface.

In the average adult brain, for example, if the cortex of one side – or hemisphere – was unfolded and flattened out it would have a surface area of about 100,000 mm2, roughly one and a half times the size of a piece of A4 paper.

Previous research has shown that folding of the cortex across mammalian species follows a universal law – that is, regardless of size and shape, they all fold in the same way.

However, until now there has been no systematic study demonstrating that the same law holds within a species.

“Our study has shown that we can use this same law to study changes in the human brain,” explains Dr Wang, based in Newcastle University’s world-leading School of Computing Science.

“From this, we identified a parameter that decreases with age, which we interpret as changing the tension on the cortical surface. It would be similar to the skin. As we age, the tension drops and the skin starts to slacken.

“It has long been known that the size and thickness of the cortex changes with age but the existence of a general law for folding shows us how to combine these quantities into a single measure of folding that can then be compared between genders, age groups and disease states.”

Women’s brains less folded

The team also found that male and female brains differ in size, surface area, and the degree of folding. Indeed, female brains tend to be slightly less folded than male brains of the same age. Despite this, male and female brains are shown to follow exactly the same law.

“This indicates that for the first time, we have a consistent way of quantifying cortical folding in humans,” says Dr Wang.

Throughout the lifespan of healthy individuals, cortical folding changes in the same way in both men and women but in those with Alzheimer’s disease the change in the brain folding was significantly different.

She adds: “More work is needed in this area but it does suggest that the effect Alzheimer’s disease has on the folding of the brain is akin to premature ageing of the cortex.”

Contacts and sources:Dawn Tudge
Newcastle University

Citation: Source: e. Yujiang Wang, Joe Necus, Marcus Kaiser and Bruno Mota. PNAS. DOI 10.1073/pnas.1610175113 Source: d
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Research Strongly Suggests COVID-19 Virus Enters the Brain

 

A study published in Nature Neuroscience shows how spike protein crosses the blood-brain barrier.

The S1 protein likely causes the brain to release inflammatory products causing a storm in the brain, researchers said.

More and more evidence is coming out that people with COVID-19 are suffering from cognitive effects, such as brain fog and fatigue.

And researchers are discovering why. The SARS-CoV-2 virus, like many viruses before it, is bad news for the brain. In a study published Dec.16 in Nature Neuroscience, researchers found that the spike protein, often depicted as the red arms of the virus, can cross the blood-brain barrier in mice.

This strongly suggests that SARS-CoV-2, the cause of COVID-19, can enter the brain.

The spike protein, often called the S1 protein, dictates which cells the virus can enter. Usually, the virus does the same thing as its binding protein, said lead author William A. Banks, a professor of medicine at the University of Washington School of Medicine and a Puget Sound Veterans Affairs Healthcare System physician and researcher. Banks said binding proteins like S1 usually by themselves cause damage as they detach from the virus and cause inflammation.

“The S1 protein likely causes the brain to release cytokines and inflammatory products,” he said.

In science circles, the intense inflammation caused by the COVID-19 infection is called a cytokine storm. The immune system, upon seeing the virus and its proteins, overreacts in its attempt to kill the invading virus. The infected person is left with brain fog, fatigue and other cognitive issues.

Banks and his team saw this reaction with the HIV virus and wanted to see if the same was happening with SARS CoV-2.

Banks said the S1 protein in SARS-CoV2 and the gp 120 protein in HIV-1 function similarly. They are glycoproteins – proteins that have a lot of sugars on them, hallmarks of proteins that bind to other receptors. Both these proteins function as the arms and hand for their viruses by grabbing onto other receptors. Both cross the blood-brain barrier and S1, like gp120, is likely toxic to brain tissues.

“It was like dĂ©jĂ  vu,” said Banks, who has done extensive work on HIV-1, gp120, and the blood-brain barrier.

The Banks’ lab studies the blood-brain barrier in Alzheimer’s, obesity, diabetes, and HIV. But they put their work on hold and all 15 people in the lab started their experiments on the S1 protein in April. They enlisted long-time collaborator Jacob Raber, a professor in the departments of Behavioral Neuroscience, Neurology, and Radiation Medicine, and his teams at Oregon Health & Science University.

The study could explain many of the complications from COVID-19.

“We know that when you have the COVID infection you have trouble breathing and that’s because there’s infection in your lung, but an additional explanation is that the virus enters the respiratory centers of the brain and causes problems there as well,” said Banks.

Raber said in their experiments transport of S1 was faster in the olfactory bulb and kidney of males than females. This observation might relate to the increased susceptibility of men to more severe COVID-19 outcomes.

As for people taking the virus lightly, Banks has a message:

“You do not want to mess with this virus,” he said. “Many of the effects that the COVID virus has could be accentuated or perpetuated or even caused by virus getting in the brain and those effects could last for a very long time.”

This study was partially supported by a National Institute on Aging-funded COVID-19 supplement to a shared RF1 grant of Banks and Raber.​

Contacts and sources: 
Bobbi Nodell
University of Washington Health Sciences

Publication: The S1 protein of SARS-CoV-2 crosses the blood–brain barrier in mice Elizabeth M. Rhea, Aric F. Logsdon, Kim M. Hansen, Lindsey M. Williams, May J. Reed, Kristen K. Baumann, Sarah J. Holden, Jacob Raber, William A. Banks & Michelle A. Erickson Nature Neuroscience (2020) https://www.nature.com/articles/s41593-020-00771-8 http://dx.doi.org/10.1038/s41593-020-00771-8 Source: https://www.ineffableisland.com/
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