| 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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