Developing oligodendrocytes express functional GABAB receptors that stimulate cell proliferation and migration

Luyt K, Slade T, Dorward J, Durant C, Wu Y, Shigemoto R, Mundell S, Váradi A, Molnár E. 2007. Developing oligodendrocytes express functional GABAB receptors that stimulate cell proliferation and migration. Journal of Neurochemistry. 100(3), 822–840.

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Author
Luyt, Karen; Slade, Timothy P; Dorward, Jienchi J; Durant, Claire F; Wu, Yue; Shigemoto, RyuichiIST Austria ; Mundell, Stuart J; Váradi, Anikó; Molnár, Elek
Abstract
GABAB receptors (GABABRs) are involved in early events during neuronal development. The presence of GABABRs in developing oligodendrocytes has not been established. Using immunofluorescent co-localization, we have identified GABABR 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 GABAB1abcdf and GABAB2 subunits of the GABABR. Using semiquantitative PCR analysis with GABABR isoform-selective primers we found that the expression level of GABAB1abd was substantially higher in OPCs or ASTs than in DOs. In contrast, the GABAB2 isoform showed a similar level of expression in OPCs and DOs, and a significantly higher level in ASTs. This indicates that the expression of GABAB1 and GABAB2 subunits are under independent control during oligodendroglial development. Activation of GABABRs using the selective agonist baclofen demonstrated that these receptors are functionally active and negatively coupled to adenylyl cyclase. Manipulation of GABABR 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 GABABRs in oligodendrocyte development. The presence of GABABRs 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.
Publishing Year
Date Published
2007-02-01
Journal Title
Journal of Neurochemistry
Volume
100
Issue
3
Page
822 - 840
IST-REx-ID

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Luyt K, Slade T, Dorward J, et al. Developing oligodendrocytes express functional GABAB receptors that stimulate cell proliferation and migration. Journal of Neurochemistry. 2007;100(3):822-840. doi:10.1111/j.1471-4159.2006.04255.x
Luyt, K., Slade, T., Dorward, J., Durant, C., Wu, Y., Shigemoto, R., … Molnár, E. (2007). Developing oligodendrocytes express functional GABAB receptors that stimulate cell proliferation and migration. Journal of Neurochemistry. Wiley-Blackwell. https://doi.org/10.1111/j.1471-4159.2006.04255.x
Luyt, Karen, Timothy Slade, Jienchi Dorward, Claire Durant, Yue Wu, Ryuichi Shigemoto, Stuart Mundell, Anikó Váradi, and Elek Molnár. “Developing Oligodendrocytes Express Functional GABAB Receptors That Stimulate Cell Proliferation and Migration.” Journal of Neurochemistry. Wiley-Blackwell, 2007. https://doi.org/10.1111/j.1471-4159.2006.04255.x.
K. Luyt et al., “Developing oligodendrocytes express functional GABAB receptors that stimulate cell proliferation and migration,” Journal of Neurochemistry, vol. 100, no. 3. Wiley-Blackwell, pp. 822–840, 2007.
Luyt K, Slade T, Dorward J, Durant C, Wu Y, Shigemoto R, Mundell S, Váradi A, Molnár E. 2007. Developing oligodendrocytes express functional GABAB receptors that stimulate cell proliferation and migration. Journal of Neurochemistry. 100(3), 822–840.
Luyt, Karen, et al. “Developing Oligodendrocytes Express Functional GABAB Receptors That Stimulate Cell Proliferation and Migration.” Journal of Neurochemistry, vol. 100, no. 3, Wiley-Blackwell, 2007, pp. 822–40, doi:10.1111/j.1471-4159.2006.04255.x.

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