Chrdl1 Loss of Function Mutation Increases Synaptic Plasticity in Mice

Researchers here suggest that the protein chrdl1 plays an important role in the regulation of synaptic plasticity, the ability of the brain to generate new connections between neurons. Synaptic plasticity declines with age, and is important in cognitive function. There is thus considerable interest in ways to enhance plasticity, not just to turn back this aspect of aging, but also potentially as a form of enhancement therapy to improve memory or other aspects of the mind.

Researchers have shown that astrocytes - long-overlooked supportive cells in the brain - help to enable the brain's plasticity, a new role for astrocytes that was not previously known. The findings could point to ways to restore connections that have been lost due to aging or trauma. "To investigate this role, we used a lot of techniques in the lab to identify a signal made by astrocytes that's very important for brain maturation."

The signal turned out to be a protein astrocytes secrete called Chrdl1, which increases the number and maturity of connections between nerve cells, enabling the stabilization of neural connections and circuits once they finish developing. To further understand the role of Chrdl1, the team developed mouse models with the gene disabled by introduced mutations. These mice had a level of plasticity in their brains that was much higher than normal. Adult mice with the Chrdl1 mutation had brain plasticity that looked very much like that of young mice, whose brains are still in early stages of development.

Not much is known about the role of Chrdl1 in humans, but one study of a family with a Chrdl1 mutation showed they performed extremely well in memory tests. Other studies have shown the level of the gene encoding Chrdl1 is altered in schizophrenia and bipolar disorder, suggesting that Chrdl1 may have important roles in both health and disease. Future research by the team will dive deeper into the relationships between astrocytes and neurons and look for potential ways to use astrocytes as therapy. "We're interested in learning more about what the astrocytes are secreting into the brain environment and how those signals affect the brain. We plan to look at this relationship both early in development and in situations where those connections are lost and you want to stimulate repair, like after someone has had a stroke."

Link: https://www.salk.edu/news-release/brain-cells-called-astrocytes-have-unexpected-role-in-brain-plasticity/

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