Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Chronic stress induces fatal organ dysfunctions via a new neural circuit

21.08.2017

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

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 strategy at present.


Micro inflammation developed at specific sites in the brain (top panel). Pathological analysis of the stomach showed damage to tissues in the stomach (bottom right) compared to mice not under stressful conditions (bottom left).

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

MS affects an estimated 2.5 million people worldwide and causes motor dysfunction, impaired vision and gastrointestinal failures. It is an autoimmune condition of the central nervous system (CNS) mediated by immune cells called autoreactive CD4+ T cells. In EAE mouse models, these pathogenic CD4+ T cells can cause a MS-like disease when transfused intravenously to healthy mice.

In previous studies using EAE mouse models, Professor Masaaki Murakami of Hokkaido University and his colleagues revealed autoreactive CD4+ T cells cross the blood-brain barrier at specific sites and cause inflammation in the CNS including the brain and spinal cord.

The emergence of a "gateway" for autoreactive CD4+ T cells to cross the barrier was caused by regional neural activation at those sites, which is triggered by specific sensory-sympathetic interactions. They termed these phenomena as gateway reflexes and have published on at least three, the gravity-, electric-, and pain-gateway reflexes.

In the present study, the team and their collaborators in Japan and Germany investigated the possible relations between chronic stress, micro-inflammation in the brain, and stress-related 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. Cell transfer or stress alone did not cause these symptoms. Subsequent investigations revealed a complex nerve-related 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 the stressed mice. Micro-inflammation developed around specific blood vessels, and the inflamed 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 and 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 brain or 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 to happen in various brain diseases including multiple sclerosis, are a risk factor for organ dysfunctions including severe gut and heart failure.

"These results demonstrate a direct link between brain micro-inflammation and fatal gastrointestinal diseases via the establishment of a new neural pathway under stress," says Masaaki Murakami. "Micro-inflammation in the brain is also seen in Alzheimer's disease and Parkinson's disease. So it's of particular interest to investigate possible connections between brain micro-inflammations and organ dysfunctions, including those within the brain itself, in those patients."

The study was published in the journal eLife.

Media Contact

Naoki Namba
81-117-062-185

 @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

More articles from Health and Medicine:

nachricht Study tracks inner workings of the brain with new biosensor
16.08.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Foods of the future
15.08.2018 | Georg-August-Universität Göttingen

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: It’s All in the Mix: Jülich Researchers are Developing Fast-Charging Solid-State Batteries

There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.

The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Air pollution leads to cardiovascular diseases

21.08.2018 | Ecology, The Environment and Conservation

Researchers target protein that protects bacteria's DNA 'recipes'

21.08.2018 | Life Sciences

A paper battery powered by bacteria

21.08.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>