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

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  • Taito Matsuda

    (Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan)

  • Naoya Murao

    (Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
    Laboratory of Gene Regulation Research, Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST))

  • Yuki Katano

    (Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
    Laboratory of Gene Regulation Research, Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST))

  • Berry Juliandi

    (Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
    Bogor Agricultural University)

  • Jun Kohyama

    (School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan)

  • Shizuo Akira

    (Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, Osaka University
    Research Institute for Microbial Diseases, Osaka University)

  • Taro Kawai

    (Laboratory of Molecular Immunobiology, Graduate School of Biological Sciences, NAIST)

  • Kinichi Nakashima

    (Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan)

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.

Suggested Citation

  • Taito Matsuda & Naoya Murao & Yuki Katano & Berry Juliandi & Jun Kohyama & Shizuo Akira & Taro Kawai & Kinichi Nakashima, 2015. "TLR9 signalling in microglia attenuates seizure-induced aberrant neurogenesis in the adult hippocampus," Nature Communications, Nature, vol. 6(1), pages 1-10, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7514
    DOI: 10.1038/ncomms7514
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