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Developing oligodendrocytes express functional GABA B receptors that stimulate cell proliferation and migration
Author(s) -
Luyt Karen,
Slade Timothy P.,
Dorward Jienchi J.,
Durant Claire F.,
Wu Yue,
Shigemoto Ryuichi,
Mundell Stuart J.,
Váradi Anikó,
Molnár Elek
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04255.x
Subject(s) - gabab receptor , gabaa receptor , oligodendrocyte , receptor , gene isoform , microbiology and biotechnology , baclofen , adenylyl cyclase , biology , chemistry , agonist , neuroscience , biochemistry , myelin , central nervous system , gene
GABA B receptors (GABA B Rs) are involved in early events during neuronal development. The presence of GABA B Rs in developing oligodendrocytes has not been established. Using immunofluorescent co‐localization, we have identified GABA B R proteins in O4 marker‐positive oligodendrocyte precursor cells (OPCs) in 4‐day‐old mouse brain periventricular white matter. In culture, OPCs, differentiated oligodendrocytes (DOs) and type 2 astrocytes (ASTs) express both the GABA B1abcdf and GABA B2 subunits of the GABA B R. Using semiquantitative PCR analysis with GABA B R isoform‐selective primers we found that the expression level of GABA B1abd was substantially higher in OPCs or ASTs than in DOs. In contrast, the GABA B2 isoform showed a similar level of expression in OPCs and DOs, and a significantly higher level in ASTs. This indicates that the expression of GABA B1 and GABA B2 subunits are under independent control during oligodendroglial development. Activation of GABA B Rs using the selective agonist baclofen demonstrated that these receptors are functionally active and negatively coupled to adenylyl cyclase. Manipulation of GABA B R activity had no effect on OPC migration in a conventional agarose drop assay, whereas baclofen significantly increased OPC migration in a more sensitive transwell microchamber‐based assay. Exposure of cultured OPCs to baclofen increased their proliferation, providing evidence for a functional role of GABA B Rs in oligodendrocyte development. The presence of GABA B Rs in developing oligodendrocytes provides a new mechanism for neuronal–glial interactions during development and may offer a novel target for promoting remyelination following white matter injury.