学術雑誌論文 Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit

Arima, Yasunobu  ,  Ohki, Takuto  ,  Nishikawa, Naoki  ,  Higuchi, Kotaro  ,  Ota, Mitsutoshi  ,  Tanaka, Yuki  ,  Nio-Kobayashi, Junko  ,  Elfeky, Mohamed  ,  Sakai, Ryota  ,  Mori, Yuki  ,  Kawamoto, Tadafumi  ,  Stofkova, Andrea  ,  Sakashita, Yukihiro  ,  Morimoto, Yuji  ,  Kuwatani, Masaki  ,  Iwanaga, Toshihiko  ,  Yoshioka, Yoshichika  ,  Sakamoto, Naoya  ,  Yoshimura, Akihiko  ,  Takiguchi, Mitsuyoshi  ,  Sakoda, Saburo  ,  Prinz, Marco  ,  Kamimura, Daisuke  ,  Murakami, Masaaki

6p.e25517 , 2017-08-15 , eLife Sciences Publications
ISSN:2050-084X
内容記述
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.
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https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/67390/1/elife-25517-v1.pdf

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