ミクログリアによる脳の恒常性維持とその破綻としての脳疾患

抄録

Microglia are brain-resident macrophages that prune synapses through "find me" and "eat me" signals, which are fundamental to neural circuit reorganization. While Complement C1q has been identified as a "find me" and "eat me" signal for microglia, it can be randomly distributed in the brain parenchyma under certain circumstances, such as neonatal seizures. To investigate the mechanisms by which microglia determine which synapses to phagocytose after neonatal seizures, a live imaging system for microglia-synapse interactions was established in vitro. We found that microglia contacted and engulfed more active synapses when the neurons were activated. In a mouse model of neonatal febrile seizures, inhibitory, but not excitatory, synapses were pruned by microglia, resulting in hyperactivity of dentate neuronal circuits. We also discovered that the increased activity of dentate inhibitory neurons during hyperthermia-induced seizures resulted in preferential interactions between microglia and inhibitory synapses. These findings suggest that C1q may serve as an "eat-me" and increased neuronal activity as a "find-me" signal in the process of synaptic pruning by microglia, which may underlie the development of epilepsy following neonatal seizures.