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

作者：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 Toshihihiko; Yoshioka Yoshichika; Sakamoto Naoya; Yoshimura Akihiko; Takiguchi Mitsuyoshi; Sakoda Saburo; Prinz Marco; Kamimura Daisuke; Murakami Masaaki

来源：eLife, 2017, 6: e25517.

DOI：10.7554/eLife.25517

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-ofhypothalamus, 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.

• 出版日期2017-8-15
• 单位河北医科大学