Endogenous Circadian Clock Machinery in Cortical NG2-Glia Regulates Cellular Proliferation

Abstract

AbstractThe molecular circadian clock can be found throughout the body and is essential for the synchronizing cellular physiology with the 24 h 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 in a 24 h period, including the critical clock componentBmal1RNA and BMAL1 protein. Interestingly, daily NG2-glia proliferation preferentially occurs during the time of day in whichBmal1expression is high, while conditional knockout ofBmal1decreases both cortical NG2-glia density and cellular proliferation. Furthermore, in a neurotrauma model, we show that pathology-induced NG2-glia proliferation is also dependent onBmal1expression. Because circadian rhythm disturbances are common in neurologic disorders across the life span, including in traumatic brain injury, these findings bear significant implications for cellular regeneration in brain injuries and disease.