TLR9 signalling in microglia attenuates seizure-induced aberrant neurogenesis in the adult hippocampus

Pathological conditions such as epilepsy cause misregulation of adult neural stem/progenitor populations in the adult hippocampus in mice, and the resulting abnormal neurogenesis leads to impairment in learning and memory. However, how animals cope with abnormal neurogenesis remains unknown. Here we show that microglia in the mouse hippocampus attenuate convulsive seizure-mediated aberrant neurogenesis through the activation of Toll-like receptor 9 (TLR9), an innate immune sensor known to recognize microbial DNA and trigger inflammatory responses. We found that microglia sense self-DNA from degenerating neurons following seizure, and secrete tumour necrosis factor-α, resulting in attenuation of aberrant neurogenesis. Furthermore, TLR9 deficiency exacerbated seizure-induced cognitive decline and recurrent seizure severity. Our findings thus suggest the existence of bidirectional communication between the innate immune and nervous systems for the maintenance of adult brain integrity.
Epileptic seizures generate aberrant neurogenesis in the adult mouse hippocampal region but how animals cope with abnormal neurogenesis remains unknown. Here the authors show that microglia are activated through TLR9 signaling and that this leads to sustained expression of TNF-α which attenuates induced aberrant neurogenesis.