How the circadian clock helps the brain recover after injury

Summary: NG2-glia, a newly discovered brain cell type that can self-renew, is regulated by circadian rhythms. The findings shed new light on how the body’s circadian clock can promote healing after traumatic brain injury.

Source: National Children’s Hospital

A type of brain cell that can renew itself is regulated by circadian rhythms, providing significant insight into how the body’s internal clock can promote healing after traumatic brain injury (TBI), according to new research from the National Hospital Children’s

Published in the last issue of eNeuro, the findings open new avenues of research for future TBI therapies. Currently, these injuries are managed only with supportive care and rehabilitation, rather than targeted drug treatment options.

The findings also underscore the importance of addressing circadian disruptions to help heal injured brains.

Many of the body’s cells follow a 24-hour rhythm driven by their genes known as the circadian clock. The Children’s National research team found that a relatively recently discovered type of brain cell, known as NG2-glia, or oligodendrocyte precursor cells, also follows a circadian rhythm. This cell type is one of the few that is continuously renewed throughout adulthood and is markedly proliferative during the first week after brain injury.

“We found evidence for the role of this well-known molecular pathway, the molecular circadian clock, in regulating the ability of these NG2 glia to proliferate, both at rest and after injury,” said Terry Dean, MD, Ph.D. ., a critical care specialist at Children’s National and lead author of the paper.

“This will serve as a starting point to further investigate pathways to control cell regeneration and optimize recovery after injury.”

Sometimes called the “silent epidemic,” TBI affects approximately 69 million people worldwide each year, with injuries ranging from mild concussions to severe injuries that cause death or lifelong disability.

Many of the body’s cells follow a 24-hour rhythm driven by their genes known as the circadian clock. The image is in the public domain

In the United States alone, approximately 2.8 million people suffer from TBI annually, including 630,000 children. TBI is the leading cause of death in people under the age of 45, and those who survive are often left with persistent physical, cognitive and psychological disabilities.

However, no targeted therapies exist for TBI, creating a critical need to uncover mechanisms that could unlock the regeneration of these NG2-glia cells, which are the most common brain cell type which is known to proliferate and self-renew in adult brains.

“It is essential that researchers know that cellular turnover is coordinated with the time of day,” said Vittorio Gallo, Ph.D., interim academic director and interim director of the National Children’s Research Institute. “With this knowledge, we can delve deeper into the body’s genetic healing process to understand how cells regulate and regenerate.”

About this TBI research news

Author: Katie Shrader
Source: National Children’s Hospital
Contact: Katie Shrader – National Children’s Hospital
Image: The image is in the public domain

Original Research: Closed access
“Endogenous circadian clock machinery in cortical NG2 glia regulates cell proliferation” by Terry Dean et al. eNeuro

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Endogenous circadian clock machinery in cortical NG2 glia regulates cell proliferation

The molecular circadian clock can be found throughout the body and is essential for the synchronization of cellular physiology with the 24-hour day. However, the role of the clock in regulating the regenerative potential of the brain has not been explored.

We report here that murine NG2-glia, the largest population of proliferative cells in the mature central nervous system, rhythmically express circadian clock genes over a 24-h period, including the critical clock component. Bmal1 BMAL1 RNA and protein.

Interestingly, diurnal proliferation of NG2-glia occurs preferentially during the time of day when Bmal1 expression is high, while the conditional knockout (CKO) of Bmal1 decreases both cortical NG2-glia density and cell proliferation.

Furthermore, in a model of neurotrauma, we show that pathology-induced NG2-glia proliferation is also dependent on Bmal1 expression

Because circadian rhythm disturbances are common in neurological disorders across the lifespan, including TBI, these findings have significant implications for cellular regeneration in brain injury and disease.

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