Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit
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...
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eLife Sciences Publications Ltd
2017-08-01
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Online Access: | https://elifesciences.org/articles/25517 |
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author | 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 Takiguchi Saburo Sakoda Marco Prinz Daisuke Kamimura Masaaki Murakami |
author_facet | 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 Takiguchi Saburo Sakoda Marco Prinz Daisuke Kamimura Masaaki Murakami |
author_sort | Yasunobu Arima |
collection | DOAJ |
description | 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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format | Article |
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institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-12T12:16:44Z |
publishDate | 2017-08-01 |
publisher | eLife Sciences Publications Ltd |
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series | eLife |
spelling | doaj.art-6445d973bd714f3daf24e52765425cf72022-12-22T03:33:25ZengeLife Sciences Publications LtdeLife2050-084X2017-08-01610.7554/eLife.25517Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuitYasunobu Arima0Takuto Ohki1Naoki Nishikawa2Kotaro Higuchi3Mitsutoshi Ota4Yuki Tanaka5Junko Nio-Kobayashi6Mohamed Elfeky7Ryota Sakai8Yuki Mori9Tadafumi Kawamoto10Andrea Stofkova11https://orcid.org/0000-0002-6579-6578Yukihiro Sakashita12Yuji Morimoto13Masaki Kuwatani14Toshihiko Iwanaga15Yoshichika Yoshioka16Naoya Sakamoto17Akihiko Yoshimura18Mitsuyoshi Takiguchi19Saburo Sakoda20Marco Prinz21Daisuke Kamimura22Masaaki Murakami23https://orcid.org/0000-0001-7159-7279Division of Psychoimmunology, Institute for Genetic Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, JapanDivision of Psychoimmunology, Institute for Genetic Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, JapanDivision of Psychoimmunology, Institute for Genetic Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Department of Anesthesiology and Critical Care Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, JapanDivision of Psychoimmunology, Institute for Genetic Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, JapanDivision of Psychoimmunology, Institute for Genetic Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, JapanDivision of Psychoimmunology, Institute for Genetic Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, JapanLaboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, Sapporo, JapanDivision of Psychoimmunology, Institute for Genetic Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Department of Biochemistry, Faculty of Veterinary Medicine, Alexandria University, Behera, EgyptDepartment of Microbiology and Immunology, Keio University School of Medicine, Tokyo, JapanLaboratory of Biofunctional Imaging, WPI Immunology Frontier Research Center, Osaka University, Osaka, JapanRadioisotope Research Institute, Department of Dental Medicine, Tsurumi University, Yokohama, JapanDivision of Psychoimmunology, Institute for Genetic Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, JapanDivision of Psychoimmunology, Institute for Genetic Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, JapanDepartment of Anesthesiology and Critical Care Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, JapanDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, JapanLaboratory of Histology and Cytology, Graduate School of Medicine, Hokkaido University, Sapporo, JapanLaboratory of Biofunctional Imaging, WPI Immunology Frontier Research Center, Osaka University, Osaka, JapanDepartment of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, JapanDepartment of Microbiology and Immunology, Keio University School of Medicine, Tokyo, JapanLaboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, JapanDepartment of Neurology, National Hospital Organization Toneyama National Hospital, Osaka, JapanInstitute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg im Breisgau, GermanyDivision of Psychoimmunology, Institute for Genetic Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, JapanDivision of Psychoimmunology, Institute for Genetic Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, JapanImpact 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.https://elifesciences.org/articles/25517brain micro-inflammationorgan functionEAEmultiple sclerosisneurodegenerative disease |
spellingShingle | 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 Takiguchi Saburo Sakoda Marco Prinz Daisuke Kamimura Masaaki Murakami Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit eLife brain micro-inflammation organ function EAE multiple sclerosis neurodegenerative disease |
title | Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit |
title_full | Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit |
title_fullStr | Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit |
title_full_unstemmed | Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit |
title_short | Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit |
title_sort | brain micro inflammation at specific vessels dysregulates organ homeostasis via the activation of a new neural circuit |
topic | brain micro-inflammation organ function EAE multiple sclerosis neurodegenerative disease |
url | https://elifesciences.org/articles/25517 |
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