TLR9 signalling in microglia attenuates seizure-induced aberrant neurogenesis in the adult hippocampus.
TLR9 signalling in microglia attenuates seizure-induced aberrant neurogenesis in the adult hippocampus.
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DOI：
10.1038/ncomms7514
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发表时间：
2015-03-09
影响因子：
16.6
通讯作者：
Nakashima, Kinichi
中科院分区：
文献类型：
--
作者：
Matsuda, Taito;Murao, Naoya;Katano, Yuki;Juliandi, Berry;Kohyama, Jun;Akira, Shizuo;Kawai, Taro;Nakashima, Kinichi
癫痫等病理条件会导致成年小鼠海马区成年神经干/祖细胞数量的失调，从而导致神经发生的异常，导致学习和记忆障碍。然而，动物如何应对异常的神经发生仍是未知的。在这里，我们展示了小鼠海马区的小胶质细胞通过激活Toll样受体9(TLR9)来减弱惊厥发作介导的异常神经发生，TLR9是一种已知识别微生物DNA并触发炎症反应的先天免疫传感器。我们发现，小胶质细胞从癫痫发作后变性的神经元中感觉到自我DNA，并分泌肿瘤坏死因子-α，导致异常神经发生的减弱。此外，TLR9缺乏加剧了癫痫诱发的认知功能下降和反复发作的严重程度。因此，我们的发现表明，先天免疫系统和神经系统之间存在双向通讯，以维持成人大脑的完整性。癫痫发作会在成年小鼠的海马区产生异常的神经发生，但动物如何应对异常的神经发生仍不清楚。在这里，作者表明，小胶质细胞是通过TLR9信号被激活的，这导致肿瘤坏死因子-α的持续表达，从而减弱了诱导的异常神经发生。
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.
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影响因子：
4.3
作者：
Gebara E;Sultan S;Kocher-Braissant J;Toni N
通讯作者：
Toni N
影响因子：
5.3
作者：
Avignone, Elena;Ulmann, Lauriane;Audinat, Etienne
通讯作者：
Audinat, Etienne
影响因子：
5.3
作者：
Liu, Hsin-Yu;Hong, Yun-Fen;Hsueh, Yi-Ping
通讯作者：
Hsueh, Yi-Ping
影响因子：
6.2
作者：
Laird MD;Shields JS;Sukumari-Ramesh S;Kimbler DE;Fessler RD;Shakir B;Youssef P;Yanasak N;Vender JR;Dhandapani KM
通讯作者：
Dhandapani KM
影响因子：
5.3
作者：
Iosif, Robert E.;Ekdahl, Christine T.;Lindvall, Olle
通讯作者：
Lindvall, Olle