1. Developing oligodendrocytes express functional GABA(B) receptors that stimulate cell proliferation and migration.
- Author
-
Luyt K, Slade TP, Dorward JJ, Durant CF, Wu Y, Shigemoto R, Mundell SJ, Váradi A, and Molnár E
- Subjects
- Adenylyl Cyclases metabolism, Animals, Animals, Newborn, Astrocytes cytology, Astrocytes metabolism, Cell Differentiation drug effects, Cell Movement drug effects, Cells, Cultured, Central Nervous System cytology, Central Nervous System metabolism, GABA Agonists pharmacology, GABA Agonists therapeutic use, GABA-B Receptor Agonists, Mice, Mice, Knockout, Nerve Regeneration drug effects, Nerve Regeneration physiology, Oligodendroglia cytology, Oligodendroglia drug effects, Protein Subunits genetics, Protein Subunits metabolism, RNA, Messenger metabolism, Receptors, GABA-B genetics, Signal Transduction drug effects, Signal Transduction physiology, Stem Cells cytology, Stem Cells drug effects, Stem Cells metabolism, gamma-Aminobutyric Acid metabolism, Cell Differentiation physiology, Cell Movement physiology, Cell Proliferation drug effects, Central Nervous System growth & development, Oligodendroglia metabolism, Receptors, GABA-B metabolism
- Abstract
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.
- Published
- 2007
- Full Text
- View/download PDF