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PMID: 15898103 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Connexin43, the major gap junction protein of astrocytes, is down-regulated in inflamed white matter in an animal model of multiple sclerosis.

Journal of neuroscience research ·Vol. 80 ·No. 6 ·2005-06-15 ·Pages 798-808

Brand-Schieber E, Werner P, Iacobas DA, Iacobas S, Beelitz M, Lowery SL, Spray DC, Scemes E

Abstract

Both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), its animal model, involve inflammatory attack on central nervous system (CNS) white matter, leading to demyelination and axonal damage. Changes in astrocytic morphology and function are also prominent features of MS and EAE. Resting astrocytes form a network that is interconnected through gap junctions, composed mainly of connexin43 (Cx43) protein. Although astrocytic gap junctional connectivity is known to be altered in many CNS pathologies, little is known about Cx43 expression in inflammatory demyelinating disease. Therefore, we evaluated the expression of Cx43 in spinal cords of EAE mice compared with healthy controls. Lumbar ventral white matter areas were heavily infiltrated with CD11beta-immunoreactive monocytes, and within these infiltrated regions loss of Cx43 immunoreactivity was evident. These regions also showed axonal dystrophy, demonstrated by the abnormally dephosphorylated heavy-chain neurofilament proteins. Astrocytes in these Cx43-depleted lesions were strongly glial fibrillary acidic protein reactive. Significant loss (38%) of Cx43 protein in EAE mouse at the lumbar portion of spinal cords was confirmed by Western blot analysis. Decreased Cx43 transcript level was also observed on cDNA microarray analysis. In addition to changes in Cx43 expression, numerous other genes were altered, including those encoding adhesion and extracellular matrix proteins. Our data support the notion that, in addition to damage of myelinating glia, altered astrocyte connectivity is a prominent feature of inflammatory demyelination.

MeSH Terms
Animals Astrocytes/metabolism Blotting, Western Connexin 43/metabolism Disease Models, Animal Down-Regulation Encephalomyelitis, Autoimmune, Experimental/metabolism,pathology Female Gap Junctions/metabolism Gene Expression Immunohistochemistry Inflammation/metabolism,pathology Mice Multiple Sclerosis/metabolism,pathology Oligonucleotide Array Sequence Analysis Spinal Cord/metabolism,pathology
Chemicals
Connexin 43
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Brand-Schieber Elimor
Department of Neurology, Albert Einstein College Medicine, Bronx, NY 10461, USA. [email protected]
Werner Peter
Iacobas Dumitru A
Iacobas Sanda
Beelitz Michelle
Lowery Stuart L
Spray David C
Scemes Eliana
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Article Info
Journal
Journal of neuroscience research
Abbr.
J Neurosci Res
ISSN
0360-4012
DOI
10.1002/jnr.20474
Email
[email protected]
Published
2005-06-15
Pages
798-808
Language
English
Region
United States
NLM ID
7600111
PMCID
PMC1226319
Subset
IM
Grants
NINDS NIH HHS · NS-41282 · United States
NINDS NIH HHS · R01 NS041282 · United States
NINDS NIH HHS · NS-41023 · United States
NINDS NIH HHS · R01 NS041056 · United States
NINDS NIH HHS · NS-41056 · United States
NINDS NIH HHS · R01 NS041023 · United States
NIMH NIH HHS · R01 MH065495 · United States
NIMH NIH HHS · MH-65495 · United States
External Links
PubMed source DOI: 10.1002/jnr.20474 PMC Full Text View journal details
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