Microglia depletion alleviates the disruptions in circadian rhythms and anxiety caused by bmal1 deficiency.

Microglia, the intrinsic immune cells of the brain, play a crucial role in maintaining neuronal health and circadian rhythms. BMAL1 is a core transcriptional regulator of the molecular circadian clock that coordinates daily rhythms in physiology and behavior. In this study, we investigated the impact of microglial modulation on circadian disruptions and behavioral abnormalities observed in bmal-/- mice. Our results revealed disruptions in circadian rhythms and microglial activation in bmal-/- mice, characterized by altered activity patterns and increased microglia numbers. Inhibiting microglia with PLX5622 effectively ameliorated circadian disruptions and improved behavioral performance in bmal-/- mice, as observed in open field and elevated plus-maze tests. Additionally, microglia inhibition restored structural and functional abnormalities in neurons of bmal-/- mice, including dendritic spine reduction and impaired long-term potentiation (LTP). Furthermore, we observed a normalization of proinflammatory cytokine levels (IL-1β and TNF-α) upon PLX5622 treatment, indicating a potential link between microglial modulation and neuroinflammation. Our findings highlight the intricate interplay between circadian rhythms, microglia, and neuronal health, offering insights into potential therapeutic interventions for circadian-related and neuroinflammatory disorders.