Microglial circadian clock regulation of microglial structural complexity, dendritic spine density and inflammatory response.
Abstract
Cortical microglia exhibit a ramified shape during sleep, while they have a hyper-ramified shape during wakefulness, which is characterized by their longer processes with increased branching points. The microglial molecular circadian clock regulates expressions of both cathepsin S (CatS) and P2Y12 receptors in the brain with a peak at zeitgeber time 14 (2 h after beginning of the dark phase). We postulated that these two microglia-specific molecules contribute to diurnal alterations of microglial shapes and neuronal activities in the cerebral cortex. During wakefulness, CatS secreted from cortical microglia may be involved in P2Y12 receptor-dependent process extension. Secreted CatS subsequently degrades the perineuronal nets, initiating the downscaling of both spine density and synaptic strength of cortical neurons toward the beginning of sleep. The downscaling of both spine density and synaptic strength of cortical neurons during sleep could improve signal-to-noise, which would benefit memory consolidation, or allow for new learning to occur during subsequent waking. Furthermore, disruption of CatS induces the sleep disturbance and impaired social interaction in mice. Moreover, the microglial clock system disruption may also ...Continue Reading
References
Dendritic spine dynamics are regulated by monocular deprivation and extracellular matrix degradation
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