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

Taito Matsuda, Naoya Murao, Yuki Katano, Berry Juliandi, Jun Kohyama, Shizuo Akira, Taro Kawai, Kinichi Nakashima

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number6514
JournalNature communications
Volume6
DOIs
Publication statusPublished - Mar 9 2015

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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