Nat Neurosci: Accident! Small glial cells are moving through the brain to stop neurons from becoming overactive

17/ ---, an important part of the brain's immune system, immune cells called small glial cells constantly stretch and retract "branches" from their cell bodies to observe their surroundings.
imagine an octopus that doesn't move its body, but extends its tentacles in all directions.
that's how small glial cells work.
in an hour, each cell will cover the entire three-dimensional space around it.
then, everything starts all over again.
this continuous and rapid monitoring is unique to small and medium-sized glial cells in the brain.
it happens all the time in your brain, whether there's a disease or not, whether you're awake or asleep.
small glial cells can also quickly branch them to damaged areas of the brain.
long-held theory that small glial cells do this surveillance to sense the invasion or trauma of infectious pathogens.
, "It never made sense to me," said Dr. Katerina Akassoglou, a senior fellow at the Gladston Institute in the United States.
why does a cell spend so much energy on something that might never happen? I've always believed that there must be another reason why small glial cells have been moving, which may well be related to the normal functioning of the brain.
"it turns out that Akassoglou is right.
photo from Nature Neuroscience, 2020, doi:10.1038/s41593-020-00756-7.
a new study, Akassoglou and his team found that monitoring small glial cells helps prevent epileptic activity, or hyperexcitation, in the brain.
given that overexcitement is a common feature of many neurological disorders, including Alzheimer's disease, epilepsy and autism, these findings could open up new avenues of treatment for these diseases.
results were published online December 14, 2020 in the journal Nature Neuroscience under the title "Microglial Gi-dependent dynamics regulation brain network hyperexcitability".
the overactive brain Akassoglou has been interested in the brain's innitable immune system since her scientific career.
first time she observed small glial cell monitoring under a microscope was in 2003 when she was a postdoctoral student and discovered the phenomenon in a nearby laboratory.
immediately realized that to understand the cells, she had to find a way to "freeze" their movements.
's easier said than done--- it took more than a decade to figure out how to stop them from moving.
there are ways to kill these cells, but then they disappear and you can't study their movements.
it's very challenging to find a way to keep them alive and stop them from investigating the brain.
and her team built the first mouse model, which blocks the process by which small glial cells monitor the brain.
cells are still alive, but they can no longer stretch and retract their branches.
, the goal of this research project is just to see what happens.
is driven purely by curiosity, " says Akassoglou, a professor at the Akassoglou.
we just want to know why these cells keep moving, and if they stop, what happens to the brain? "At first, nothing seemed to happen, and the "frozen" small glial cells seemed normal.
until one day, co-author Dr. Victoria Rafalski, a former postdoctoral scholar at the Akassoglou laboratory, accidentally observed overexcitement in a mouse's brain.
Rafaalski, said, "It was only then that we realized that mice had spontaneous seizures when small glial cells were not functioning properly.
this is the first time we have shown that monitoring of these cells may inhibit epilepsy activity.
also gives us a hint as to why they need to move constantly--- suppressing seizures may be an ongoing need in the brain.
"For further investigation, the Akassoglou team relied on the latest technological advances in microscopes and image analysis.
combined these methods to develop their own way of observing the interaction between small glial cells and active neurons in the living brain, just as mice ran on wheels while scratching their beards.
found that small glial cells do not stretch their branches at will.
, small glial cells mainly stretch one by one to active neurons, with less attention paid to inactive neurons.
important, they note that when small glial cells come into contact with an active neuron, the activity of that neuron does not increase further. "Small glial cells seem to be able to sense which neuron is about to become overactive and control it by contacting it, thereby preventing the neuron's activity from escalating," explained Mario Merlini, co-lead author of the
paper and a former researcher at the Akassoglou laboratory.
in contrast, in our mouse model, the movement of small glial cells was frozen, and we found that the activity of nearby neurons increased, a bit like a thermostat-broken heater.
this changes our thinking about how neuron activity in the brain regulates.
small glial cells are not a switch, but a thermostat in the brain that controls the excess activity of neurons.
" findings help the Akassoglou team discover the physiological role of small glial cell monitoring, which plays a crucial role in keeping neurons active or overexcited by keeping their activity within normal range.
"Excessive excitability of neural networks can be observed in people with epilepsy and in patients with other diseases that are more likely to develop epilepsy, such as Alzheimer's disease and autism," said co-author Dr. Jorge Palop, co-author of the paper and an associate researcher at the Glaston Institute.
overactive brain causes a large number of neurons to activate (or become active) at the same time, a process known as hypersynchrony, which can lead to spontaneous seizures.
our study may provide a new way to intervene in highly excitable diseases.
"<!--ewebeditor:page title"--in many brain diseases, the ability of small glial cells to investigate the brain is impaired," > Akassoglou said.
We now have a model to study the effects of damaged small glial cells on brain inflammation and cognitive abilities in diseases including Alzheimer's disease and multiple sclerosis, as well as the infection of the brain by the virus SARS-CoV-2.
"understanding that small glial cells are constantly moving to stop the brain from becoming overexcited may have therapeutic implications."
, by using drug activators to force small glial cells to stretch their branches, overactivity in the brain can be reversed.
study, this method resumed the stretching and retractation of small glial cells and restored neuron activity to normal levels.
Akasoglou and her team are now expanding the study to test any possible beneficial effects in disease models.
, "By solving the mystery of the constant movement of small glial cells, we now have new clues to treat devastating brain diseases," said Akassoglou.
" (Bioon.com) Reference: 1. Mario Merlini et al. Microglial Gi-dependent dynamics regulate brain network hyperexcitability. Nature Neuroscience, 2020, doi:10.1038/s41593-020-00756-7.2.An unexpected role for the brain's immune cells。