K+ channel blockade impairs remyelination in the cuprizone model.
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.
Bacia
Andrzej
A
Department of Neurology and Committee on Neurobiology, Brain Research Institute, University of Chicago, Chicago, Illinois 60637, USA.
Wollmann
Robert
R
Soliven
Betty
B
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002614:Chelating Agents; D003337:Corpus Callosum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D005911:Gliosis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D004676:Myelin Basic Protein / Q000187:drug effects / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
D002614:Chelating Agents; D004676:Myelin Basic Protein; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D003471:Cuprizone; D015761:4-Aminopyridine