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

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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 stressgateway 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.

Original languageEnglish
Article numbere25517
JournaleLife
Volume6
DOIs
Publication statusPublished - 2017 Aug 15

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Encephalitis
Neural Pathways
Brain
Homeostasis
Chemical activation
Networks (circuits)
Gastrointestinal Diseases
Neurons
Mediodorsal Thalamic Nucleus
Third Ventricle
T-cells
Paraventricular Hypothalamic Nucleus
Dentate Gyrus
Thalamus
Reflex
Switches
Cytokines
Inflammation
T-Lymphocytes
Injections

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Arima, Y., Ohki, T., Nishikawa, N., Higuchi, K., Ota, M., Tanaka, Y., ... Murakami, M. (2017). Brain Micro-Inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit. eLife, 6, [e25517]. https://doi.org/10.7554/eLife.25517

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.

In: eLife, Vol. 6, e25517, 15.08.2017.

Research output: Contribution to journalArticle

Arima, Y, Ohki, T, Nishikawa, N, Higuchi, K, Ota, M, Tanaka, Y, Nio-Kobayashi, J, Elfeky, M, Sakai, R, Mori, Y, Kawamoto, T, Stofkova, A, Sakashita, Y, Morimoto, Y, Kuwatani, M, Iwanaga, T, Yoshioka, Y, Sakamoto, N, Yoshimura, A, Takiguchi, M, Sakoda, S, Prinz, M, Kamimura, D & Murakami, M 2017, 'Brain Micro-Inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit', eLife, vol. 6, e25517. https://doi.org/10.7554/eLife.25517
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. / Brain Micro-Inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit. In: eLife. 2017 ; Vol. 6.
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