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Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit

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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.
Type: article
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)

Submitter: 村上 正晃

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