Neurological Night Shift: Immune Cells Rewire, Repair Our Brains As We Sleep

ROCHESTER, N.Y. — On a conscious level, sleep is an opportunity to leave our thoughts behind and rest up. But, on a subconscious level, our brains keep on working. Vivid dreams are just one prime example of the fact that our brains never really shut down. Now, new research reveals another important neurological function being taken care of while we hit the pillow: immune cells called microglia are primarily active while we sleep, reorganizing nerve cell connections, repairing damage, and fighting infections.

The study, conducted at the University of Rochester Medical Center using lab mice, will help scientists and doctors better under brain plasticity, or the human brain’s ability to change and evolve in response to experiences. Additionally, these findings have far-reaching implications in reference to diseases like autism, schizophrenia, and dementia, all of which are associated with an individual’s brain not functioning properly. This discovery also sheds some light on the human brain’s ability to fight infections and repair damage following a stroke or other major injury.

“It has largely been assumed that the dynamic movement of microglial processes is not sensitive to the behavioral state of the animal,” explains lead author Dr. Ania Majewska, a professor in the University of Rochester Medical Center’s (URMC) Del Monte Institute for Neuroscience, in a release. “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.”

Microglia are incredibly important to our brains’ wellbeing, effectively acting as emergency first responders who are always on call. They patrol the brain and spinal cord and immediately take action if they detect any infections, debris, or dead cell tissue. While scientists have known this about microglia for some time, it was discovered much more recently that these immune cells also play a big role in plasticity.

Dr. Majewska and her team are no strangers to these incredible immune cells; in prior studies they had already established how microglia interact with synapses, the meeting points where two neurons connect and communicate with one another. Microglia help facilitate these connections by maintaining the health and functioning of synapses, and ridding the brain of nerve cell connections when they are no longer needed.

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This set of research looked specifically at the role of norepinephrine, a neurotransmitter that indicates arousal and stress in the central nervous system. Norepinephrine is present in our brains as we sleep, but when our bodies produce higher levels it kickstarts our nerve cells, causing us to wake from sleep and become aware of our surroundings. This study found that norepinephrine also has an effect on the beta2 adrenergic receptor, a specific receptor in the brain that is found in high levels in microglia. When this receptor is present at high levels in the brain, microglia fall into a hibernation-like state.

To put it succinctly, the research team discovered that microglia are much more active and beneficial as we are sleeping, and tend to hibernate or become inactive while we are awake due to the presence of norepinephrine.

Researchers utilized advanced imaging technology to observe activity in the brains of live lab mice, illustrating that when the mice were exposed to high levels of norepinephrine their microglia became largely dormant and unable to treat injuries or infections.

“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,” says first author Dr. Rianne Stowell, a postdoctoral associate at URMC. “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.”

Overall, this research adds another element to the already strong argument that sleep is absolutely essential to a healthy brain and mental state. Furthermore, these discoveries may also help explain the relationship between constant lack of sleep and an increased risk of conditions like Alzheimer’s and Parkinson’s.

The study is published in the scientific journal Nature Neuroscience.

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