K+ channel blockade impairs remyelination in the cuprizone model

Glia
Andrzej BaciaBetty Soliven

Abstract

The adult CNS has the capacity to remyelinate following metabolic, toxic and autoimmune demyelinating insults. In cuprizone-induced demyelination, spontaneous remyelination occurs after the cessation of cuprizone diet. We used the cuprizone model to investigate the role of glial K(+) channels in oligodendroglial (OLG) regeneration and remyelination in vivo. We found that treatment with 4-aminopyridine (4-AP), a broad-spectrum K(+) channel antagonist, results in: (1) decreased number of oligodendroglial progenitors (OP) and OLGs; (2) diminished astrogliosis; and (3) decreased remyelination in the corpus callosum based on the immunoreactivity to myelin basic protein (MBP), Rip monoclonal antibody, and by electron microscopy. Our findings support the concept that glial K(+) channels play an important role during OLG regeneration and remyelination, a crucial factor to be considered during the development of therapeutic strategies to facilitate recovery in demyelinating diseases and spinal cord injury.

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Citations

Jan 21, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hye Jung KimBetty Soliven
May 5, 2011·Experimental and Molecular Pathology·Cosmin A TeglaHorea Rus
Jan 27, 2010·Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology·Steve VucicMatthew C Kiernan
Jan 19, 2007·Brain Research·Jeremy S TomaMatt S Ramer
Feb 9, 2005·Experimental Neurology·Hakan Aldskogius
Aug 19, 2015·Frontiers in Molecular Neuroscience·Arsalan AlizadehSoheila Karimi-Abdolrezaee
Jun 7, 2018·Cell Transplantation·Baoyou FanShiqing Feng
Apr 21, 2006·American Journal of Physiology. Cell Physiology·Seema Tiwari-WoodruffJeff Bronstein
Jul 12, 2018·CNS Drugs·Verena Isabell LeussinkHans-Peter Hartung

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