Title: Novel animal model of multiple sclerosis: The glial connexin gap junction as an environmental tuner for neuroinflammation

Abstract

Abstract Connexins, which comprise gap junctions (GJs) via homotypic/heterotypic oligomerization, act as channels to connect opposing cells, mainly in solid organs such as the skin, liver, heart, and central/peripheral nervous system. Connexins are synthesized in the endoplasmic reticulum, assembled in the Golgi apparatus as hexamers, and inserted into the cell membrane as hemichannels. These hemichannels are closed under normal conditions until they combine to form clusters and connect to neighboring cells via GJs in a head‐to‐head configuration. Opening of hemichannels, which depends on the intra‐ or extracellular environment, allows various bioactive molecules to enter into or be released from the host cells. Recent pathological studies on human demyelinating diseases have revealed alterations of connexin expression patterns in demyelinating lesions. To elucidate the molecular mechanisms of connexins in the pathomechanisms of inflammatory demyelination, we induced experimental autoimmune encephalomyelitis (EAE) in connexin 30 (Cx30)‐deficient mice, oligodendroglia‐specific Cx47‐ablated mice, and astroglia‐specific Cx43‐ablated mice. We found that both astroglial‐Cx30‐deficient mice and Cx43‐ablated mice showed amelioration of the clinical course of EAE, while oligodendroglial‐Cx47‐ablated mice showed aggravation. These findings indicate the distinct role of connexins expressed in different cell types and the substantial contribution of connexin‐mediated pathology to demyelinating disorders. The imbalance in connexin expression,more » which is caused by the inflammatory environment, results in an increase in hemichannels in glial cells. The release of proinflammatory molecules induced by the increase in hemichannels on activated glial cells is a crucial mechanism of demyelinating disorders.« less

Authors:

Yamasaki, Ryo ^[1]

---

+ Show Author Affiliations

1. Department of Neurology Neurological Institute Graduate School of Medical Sciences Kyushu University Fukuoka Japan

Publication Date:

Tue Mar 31 00:00:00 EDT 2020

Sponsoring Org.:

USDOE

OSTI Identifier:

1607803

Resource Type:

Publisher's Accepted Manuscript

Journal Name:

Clinical and Experimental Neuroimmunology

Additional Journal Information:

Journal Name: Clinical and Experimental Neuroimmunology Journal Volume: 11 Journal Issue: S1; Journal ID: ISSN 1759-1961

Publisher:

Wiley-Blackwell

Country of Publication:

Country unknown/Code not available

Language:

English