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.
Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Taito
T
Matsuda
1] Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan [2] Laboratory of Gene Regulation Research, Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), Nara 630-0192, Japan.
Naoya
N
Murao
1] Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan [2] Laboratory of Gene Regulation Research, Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), Nara 630-0192, Japan.
Yuki
Y
Katano
1] Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan [2] Department of Biology, Bogor Agricultural University, Bogor 16144, Indonesia.
Berry
0000000303485675
B
Juliandi
Department of Physiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Jun
J
Kohyama
1] Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan [2] Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Shizuo
S
Akira
Laboratory of Molecular Immunobiology, Graduate School of Biological Sciences, NAIST, Nara 630-0192, Japan.
Taro
T
Kawai
Department of Stem Cell Biology and Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Kinichi
K
Nakashima
D000818:Animals; D003071:Cognition; D060825:Cognitive Dysfunction / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D055495:Neurogenesis / Q000235:genetics / Q000276:immunology*; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012640:Seizures / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; C495370:Tlr9 protein, mouse; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha