2017/9/25

Chronic stress induces fatal organ dysfunctions via a new neural circuit

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21. 08. 2017

New research reveals the mechanisms behind the effects of chronic stress and tiny
inflammations in the brain on fatal gut failure.

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Hokkaido University researchers revealed that fatal gut failure in a multiple
sclerosis (MS) mouse model, EAE, under chronic stress is caused by a newly
discovered nerve pathway. The findings could provide a new therapeutic strategy
for the intractable disease, particularly progressive MS, which has no therapeutic

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strategy at present.
MS affects an estimated 2.5 million
people worldwide and causes motor
dysfunction, impaired vision andgastrointestinal failures. It is an
autoimmune condition of the central
nervous system (CNS) mediated byimmune cells called autoreactive
CD4+ T cells. In EAE mouse models,these pathogenic CD4+ T cells cancause a MS­like disease whentransfused intravenously to healthy
mice.

of Hokkaido University and his

Micro inflammation developed at specific sites inthe brain (top panel). Pathological analysis of thestomach showed damage to tissues in thestomach (bottom right) compared to mice notunder stressful conditions (bottom left).

colleagues revealed autoreactive

Credit: Arima Y., et al. eLife. August 15, 2017.

In previous studies using EAE mousemodels, Professor Masaaki Murakami

CD4+ T cells cross the blood­brainAnzeigebarrier at specific sites and cause
inflammation in the CNS including

Event Newsthe brain and spinal cord.

“Lasers in Composites
Symposium” in Aachen – fromScience to Application... more about:» CD4+ T cells » Hokkaido » Tcells » blood vessels» inflammation » mousemodels » neural circuit

The emergence of a "gateway" for autoreactive
CD4+ T cells to cross the barrier was caused byregional neural activation at those sites, which istriggered by specific sensory­sympatheticinteractions. They termed these phenomena as

gateway reflexes and have published on at least three, the gravity­, electric­, andpain­gateway reflexes.
In the present study, the team and their collaborators in Japan and Germany
investigated the possible relations between chronic stress, micro­inflammation in

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06.09.2017 | Event Newsthe brain, and stress­related organ failures.
They put healthy mice under stress by disturbing their sleep or by rearing them on
wet bedding. The transfer of pathogenic CD4+ T cells under the stress caused
severe symptoms such as gastrointestinal failures and even sudden death. Celltransfer or stress alone did not cause these symptoms. Subsequent investigations

find and help
to the campaign page >>>revealed a complex nerve­related mechanism behind this process.
The injected pathogenic CD4+ T cells
accumulated around blood vessels in two
specific sites at the center of the brains of thestressed mice. Micro­inflammation developedaround specific blood vessels, and theinflamed sites then released a small molecule called ATP that switched on a nerve
pathway that is normally turned off. This switch led to gut dysfunctions, bleeding

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2017/9/25

Chronic stress induces fatal organ dysfunctions via a new neural circuitand failure. Also, the bleeding led to increased levels of potassium in the blood,
which was one of factors leading to heart failure.
The team was able to prevent gut failure by suppressing inflammation in the brainor blocking nerve pathways from the brain to the gut. The results suggest that tiny
areas of inflammation around some specific vessels in the brain, which are known

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to happen in various brain diseases including multiple sclerosis, are a risk factor fororgan dysfunctions including severe gut and heart failure.
"These results demonstrate a direct link between brain micro­inflammation andVideoLinks

fatal gastrointestinal diseases via the establishment of a new neural pathway under

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stress," says Masaaki Murakami. "Micro­inflammation in the brain is also seen in
Alzheimer's disease and Parkinson's disease. So it's of particular interest toinvestigate possible connections between brain micro­inflammations and organ
dysfunctions, including those within the brain itself, in those patients."

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The study was published in the journal eLife.
Media Contact
Naoki Namba
81­117­062­185@hokkaido_uni
https://www.global.hokudai.ac.jp/

Naoki Namba | EurekAlert!

Further reports about: > CD4+ T cells > Hokkaido > T cells> blood vessels > inflammation > mouse models > neural circuit

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Chronic stress induces fatal organ dysfunctions via a new neural circuit
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