Night gardeners: Microglia involved in brain plasticity during sleep

By Samantha Black, PhD, ScienceBoard editor in chief

October 21, 2019 -- Research from the University of Rochester Medical Center (URMC) suggests that specific immune cells called microglia – which play a crucial role in reorganizing connections between nerve cells, fighting infection, and repairing damage – are primarily active during sleep. The research, conducted on mouse models, was published in Nature Neuroscience on October 21.

Microglia are a type of glial cell that is located throughout the brain and spinal cord. They are found in 10-15% of all cells within the brain and act as the first and main form of active immune defense in the central nervous system. Microglia are extremely sensitive to changes in the environment, which allows them to physically survey domains and savages foreign materials on a regular basis.

Previous research suggests that microglia also play a key role in regulating activity-dependent plasticity by removing inappropriate or excess synapses. Plasticity is the ongoing process by which complex networks and connections between neurons are wired and rewired during development and to support learning, memory, cognition, and motor function. In this process, microglia help maintain the health and function of synapses by pruning connections that are no longer necessary for brain function.

The current study, the authors suggest that microglial surveillance is reduced in awake mice compared to anesthetized mice, suggesting that arousal state modulates microglial function. Norepinephrine, a neurotransmitter that signals arousal and stress, is implicated with acting on beta2 adrenergic receptor. This receptor is highly expressed in microglia cells and when norepinephrine is present in the brain, microglia slip into inactivity.

"It has largely been assumed that the dynamic movement of microglial processes is not sensitive to the behavioral state of the animal," said Ania Majewska, PhD, a professor in the URMC Del Monte Institute for Neuroscience and lead author of the study. "This research shows that the signals in our brain that modulate the sleep and awake state also act as a switch that turns the immune system off and on."

This research could have implications for brain plasticity in diseases like autism spectrum disorders, schizophrenia, and dementia. These diseases arise when the brain's networks are not properly maintained, and the brain becomes unable to fight off infection or repair damage. Understanding how exactly the brain's primary immune system functions is critical to developing targeted therapies and improving quality of life for patients.

"This work suggests that the enhanced remodeling of neural circuits and repair of lesions during sleep may be mediated in part by the ability of microglia to dynamically interact with the brain," said Rianne Stowell, PhD, a postdoctoral associate at URMC and first author of the paper. "Altogether, this research also shows that microglia are exquisitely sensitive to signals that modulate brain function and that microglial dynamics and functions are modulated by the behavioral state of the animal."'

The research presenting in this study reinforces the important relationship between sleep and brain health. It could even help scientists understand the connection between sleep disturbances and the onset of neurodegenerative conditions like Alzheimer's and Parkinson's diseases.

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