TY - JOUR TI - Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit AU - Arima, Yasunobu AU - Ohki, Takuto AU - Nishikawa, Naoki AU - Higuchi, Kotaro AU - Ota, Mitsutoshi AU - Tanaka, Yuki AU - Nio-Kobayashi, Junko AU - Elfeky, Mohamed AU - Sakai, Ryota AU - Mori, Yuki AU - Kawamoto, Tadafumi AU - Stofkova, Andrea AU - Sakashita, Yukihiro AU - Morimoto, Yuji AU - Kuwatani, Masaki AU - Iwanaga, Toshihiko AU - Yoshioka, Yoshichika AU - Sakamoto, Naoya AU - Yoshimura, Akihiko AU - Takiguchi, Mitsuyoshi AU - Sakoda, Saburo AU - Prinz, Marco AU - Kamimura, Daisuke AU - Murakami, Masaaki A2 - Rath, Satyajit VL - 6 PY - 2017 DA - 2017/08/15 SP - e25517 C1 - eLife 2017;6:e25517 DO - 10.7554/eLife.25517 UR - https://doi.org/10.7554/eLife.25517 AB - 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. KW - brain micro-inflammation KW - organ function KW - EAE KW - multiple sclerosis KW - neurodegenerative disease JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -