Clearing Microglia Reverses Age-Related Disruption of Sleeping Patterns in Mice
Microglia are innate immune cells of the central nervous system. They are analogous to macrophages in the rest of the body, but undertake additional duties relating to the function of neurons and in brain tissue. Microglia become overly active and inflammatory with age, reacting to the molecular damage of aging and growing numbers of senescent cells. Numerous lines of evidence suggest that this change in microglia behavior is a significant contributing cause of neurodegeneration. Fortunately, microglia can be near entirely cleared via CSF1R inhibitor drugs, triggering repopulation of the brain with new microglia that exhibit fewer issues, even in later life. This may be the basis for therapies for a range of issues in the aging brain, including sleep disruption, as noted here.
Changes in wake/sleep architecture have been observed in both aged human and animal models, presumably due to various functional decay throughout the aging body particularly in the brain. Microglia have emerged as a modulator for wake/sleep architecture in the adult brain, and displayed distinct morphology and activity in the aging brain. However, the link between microglia and age-related wake/sleep changes remains elusive. In this study, we systematically examined the brain vigilance and microglia morphology in aging mice (3, 6, 12, and 18 months old), and determined how microglia affect the aging-related wake/sleep alterations in mice.
We found that from young adult to aged mice there was a clear decline in stable wakefulness at nighttime, and a decrease of microglial processes length in various brain regions involved in wake/sleep regulation. The decreased stable wakefulness can be restored following the time course of microglia depletion and repopulation in the adult brain. Microglia repopulation in the aging brain restored age-related decline in stable wakefulness. Taken together, our findings suggest a link between aged microglia and deteriorated stable wakefulness in aged brains.
07/10/2024 Wednesday
It is known. As the lead microphage in brain, microglia clears certain pathogen infiltrations in the human body. Also, for normal healthy brain, during Slow Wave phase 3 Sleep, glymphatic system clears waste via by wave activated pressure differential pumping action, separate from heart's pumping of blood. But what role does microglia play during phase 3 Waste clearing stage ?