Title: | Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit |
Authors: | Arima, Yasunobu Browse this author |
Ohki, Takuto Browse this author |
Nishikawa, Naoki Browse this author |
Higuchi, Kotaro Browse this author |
Ota, Mitsutoshi Browse this author |
Tanaka, Yuki Browse this author |
Nio-Kobayashi, Junko Browse this author →KAKEN DB |
Elfeky, Mohamed Browse this author |
Sakai, Ryota Browse this author |
Mori, Yuki Browse this author →KAKEN DB |
Kawamoto, Tadafumi Browse this author →KAKEN DB |
Stofkova, Andrea Browse this author |
Sakashita, Yukihiro Browse this author |
Morimoto, Yuji Browse this author →KAKEN DB |
Kuwatani, Masaki Browse this author →KAKEN DB |
Iwanaga, Toshihiko Browse this author →KAKEN DB |
Yoshioka, Yoshichika Browse this author →KAKEN DB |
Sakamoto, Naoya Browse this author →KAKEN DB |
Yoshimura, Akihiko Browse this author →KAKEN DB |
Takiguchi, Mitsuyoshi Browse this author →KAKEN DB |
Sakoda, Saburo Browse this author →KAKEN DB |
Prinz, Marco Browse this author |
Kamimura, Daisuke Browse this author →KAKEN DB |
Murakami, Masaaki Browse this author →KAKEN DB |
Issue Date: | 15-Aug-2017 |
Publisher: | eLife Sciences Publications |
Journal Title: | Elife |
Volume: | 6 |
Start Page: | e25517 |
Publisher DOI: | 10.7554/eLife.25517 |
Abstract: | Impact of stress on diseases including gastrointestinal failure is well-known, but molecular mechanism is not understood. Here we show underlying molecular mechanism using EAE mice. Under stress conditions, EAE caused severe gastrointestinal failure with high-mortality. Mechanistically, autoreactive-pathogenic CD4+ T cells accumulated at specific vessels of boundary area of third-ventricle, thalamus, and dentate-gyrus to establish brain micro-inflammation via stress-gateway reflex. Importantly, induction of brain micro-inflammation at specific vessels by cytokine injection was sufficient to establish fatal gastrointestinal failure. Resulting micro-inflammation activated new neural pathway including neurons in paraventricular-nucleus, dorsomedial-nucleus-of-hypothalamus, and also vagal neurons to cause fatal gastrointestinal failure. Suppression of the brain micro-inflammation or blockage of these neural pathways inhibited the gastrointestinal failure. These results demonstrate direct link between brain micro-inflammation and fatal gastrointestinal disease via establishment of a new neural pathway under stress. They further suggest that brain micro-inflammation around specific vessels could be switch to activate new neural pathway(s) to regulate organ homeostasis. |
Rights: | http://creativecommons.org/licenses/by/4.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/67390 |
Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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