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More MS news articles for April 2003

Expression and regulation of voltage-gated sodium channel beta1 subunit protein in human gliosis-associated pathologies

Acta Neuropathol (Berl) 2003 May;105(5):515-23
Aronica E, Troost D, Rozemuller AJ, Yankaya B, Jansen GH, Isom LL, Gorter JA.
Department of (Neuro)Pathology, H2, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

Auxiliary beta1 subunits of voltage-gated sodium channels (NaChs) critically regulate channel activity and may also act as cell adhesion molecules (CAMs).

In a recent study we have shown that the expression of beta1 NaCh protein is increased in reactive astrocytes in a rat epilepsy model of mesial temporal lobe epilepsy.

The present study was undertaken to examine whether changes of NaCh beta1 subunit protein expression are also associated with structural changes occurring in human reactive astrocytes under different pathological conditions in vivo, as well as in response to changing environmental conditions in vitro.

Strong beta1 astroglial immunoreactivity was present in human brain tissue from patients with astrogliosis.

The over-expression of beta1 protein in reactive glia was observed in both epilepsy-associated brain pathologies (temporal lobe epilepsy, cortical dysplasia), as well as non-epileptic (cerebral infarction, multiple sclerosis, amyotrophic lateral sclerosis, meningo-encephalitis) disorders.

The up-regulation of beta1 subunit protein in astrocytes can be reproduced in vitro.

beta1 protein is highly expressed in human astrocytes cultured in the presence of trophic factors, under conditions in which they show morphology similar to the morphology of cells undergoing reactive gliosis.

The growth factor-induced overexpression of beta1 protein was abrogated by PD98059, which inhibits the mitogen-activated protein kinase pathway.

These findings demonstrate that the expression of NaCh beta1 subunit protein in astrocytes is plastic, and indicate a novel mechanism for modulation of glial function in gliosis-associated pathologies.