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

First Author  Matsuda T Year  2015
Journal  Nat Commun Volume  6
Pages  6514 PubMed ID  25751136
Mgi Jnum  J:221896 Mgi Id  MGI:5641808
Doi  10.1038/ncomms7514 Citation  Matsuda T, et al. (2015) TLR9 signalling in microglia attenuates seizure-induced aberrant neurogenesis in the adult hippocampus. Nat Commun 6:6514
abstractText  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-alpha, 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.
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