Nonapoptotic caspase-3 guides C1q-dependent synaptic phagocytosis by microglia.

ABSTRACT: Caspases are known to mediate neuronal apoptosis during brain development. However, here we show that nonapoptotic activation of caspase-3 at presynapses drives microglial synaptic phagocytosis. Real-time observation and spatiotemporal manipulation of synaptic caspase-3 in the newly established, mouse-derived culture system demonstrate that increased neuronal activity triggers localized presynaptic caspase-3 activation, facilitating synaptic tagging by complements. High-resolution live imaging reveals that caspase-3 activation promotes synapse-selective complement-dependent microglial phagocytosis without axonal shearing. Furthermore, activity-dependent caspase-3 activation at inhibitory presynapses induces microglial phagocytosis in mice and increases seizure susceptibility. This increase

SUBMITTER: Andoh M 

PROVIDER: S-EPMC11754728 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature