How the circadian clock helps the brain recover after injury

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

Source: National Children’s Hospital

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

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

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

Many of the body’s cells follow a 24-hour rhythm controlled by their genes known as the circadian clock. The Children’s National research team found that a relatively newly 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 continuously renews itself during adulthood and is particularly proliferative in 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. ., intensive care specialist at Children’s National and the lead author of the paper.

“This will serve as a starting point to further explore avenues to control cellular regeneration and optimize recovery from injury.”

TBI, also referred to as “the silent epidemic,” affects an estimated 69 million people worldwide each year, with injuries ranging from minor concussions to serious injuries causing death or lifelong disability.

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

In the United States alone, approximately 2.8 million people contract TBI each year, 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.

Yet targeted therapies for TBI do not exist, raising a critical need to uncover the mechanisms that could unlock the regeneration of these NG2 glial cells, the most abundant type of brain cell known to proliferate and self-regulate. renew in adult brain.

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

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 machines in cortical NG2 glia regulate cellular proliferation” by Terry Dean et al. eNeuro

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Abstract

Endogenous circadian clock machines in cortical NG2 glia regulate cellular proliferation

The molecular circadian clock is 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 studied.

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

Interestingly, the daily proliferation of NG2 glia preferentially occurs at the time of day when: Bmal1 expression is high, while conditional knockout (CKO) of Bmal1 decreases both cortical NG2 glia density and cellular proliferation.

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

Because circadian arrhythmias are common in neurological disorders throughout life, including TBI, these findings have significant implications for cellular regeneration in brain injury and disease.

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