Neurons in the brain tend to get most of the scientific attention, but a set of cells around them called astrocytes — literally star-shaped cells — are increasingly seen as crucial actors in the time to guide a brain to organize itself properly.
Specifically, astrocytes, which make up about half the mass of a human brain, appear to guide the formation of synapses, the connections between neurons that form and reshape as we learn and remember.
A new study by Duke and UNC scientists has discovered a crucial protein involved in communication and coordination between astrocytes as they build synapses. Lacking this molecule, called hepaCAM, astrocytes are not as sticky as they should be and tend to adhere to themselves rather than form connections with their fellow astrocytes.
This finding, in studies on mice with the hepaCAM gene removed from its astrocytes, is an important clue in efforts to understand several brain disorders, including cognitive disorders, epilepsy and autism spectrum. The play appears in the magazine on June 24 Neuron.
A rare disorder called megalencephalic leukoencephalopathy (MLC) is also known to be caused by a mutation in the hepaCAM gene, and this work may provide answers about what exactly has failed. MLC is a progressively worsening developmental disorder, causing macrocephaly (a large head), inflammation of the white matter in the brain, intellectual disability, and epilepsy.
By selectively removing hepaCAM from astrocytes to see what it does, “we turn cells into introverts,” said lead author Cagla Eroglu, an associate professor of cell biology at Duke University School of Medicine. “They usually want to get there, but without hepaCAM they started hugging.”
“If the file astrocyte make connections with your neighbors and then start having a network, “Eroglu said.” To make a brain functional, you need a functional astrocytic network. “
The researchers focused on hepaCAM looking for genes that are highly active in astrocytes and involved in brain dysfunction. They were associated with another group working at hepaCAM at the University of Barcelona, but this group has been studying the molecule for its role in regulating chloride signaling channels in astrocytes.
The Duke group found that removing hepaCAM from astrocytes led to a synaptic network that excited too easily and was not as well cushioned. “The effect on inhibitory synapses was the strongest,” said first author Katie Baldwin, who recently became an assistant professor of cell biology and physiology at the University of North Carolina at Chapel Hill. “You’re putting inhibition and arousal up, so you can really point to an epilepsy mechanism.”
Baldwin, who did this work as a postdoctoral researcher at Eroglu’s lab, plans to continue these questions in his new UNC lab, checking to see if hepaCAM-deficient mice behave differently or have changes in learning and memory or if they present with stress. and social anxiety that are a marker of it autism spectrum disorders. He said they could also reintroduce mutation versions of the protein into mice that were born without it to see what effects it has.
“We know that hepaCAM interacts with itself between two astrocytes, but we don’t know what it interacts with at the synapse,” Baldwin said. “We don’t know if it could interact with hepaCAM that is also found in neurons or if it could be some other protein that we don’t know yet.”
Katherine T. Baldwin et al, HepaCAM controls the self-organization and assembly of astrocytes, Neuron (2021). DOI: 10.1016 / j.neuron.2021.05.025
Duke University School of Nursing
Citation: Researchers find the adhesions that build brain networks (2021, June 24) recovered on June 25, 2021 at https://medicalxpress.com/news/2021-06-adhesions-brain-networks.html
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