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Profile of changes in gene expression in cultured hippocampal neurones evoked by the GABA_B receptor agonist baclofen

¹ Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University of Bristol, Bristol, United Kingdom
² DNA Array Unit, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland

Metabotropic -aminobutyric acid receptors (GABA_BRs) play a critical role in inhibitory synaptic transmission in the hippocampus. However, little is known about a possible long-term effect requiring transcriptional changes. Here, using microarray technology and RT-PCR of RNA from cultured rat embryonic hippocampal neurones, we report the profile of genes that are up- or downregulated by activation of GABA_BRs by baclofen but are not changed by baclofen in the presence of the GABA_BR antagonist CGP-55845A. Our data show, for the first time, regulation of transcription of defined mRNAs after specific GABA_B receptor activation. The identified genes can be grouped into those encoding signal transduction, endocytosis/trafficking, and structural classes of proteins. For example, butyrylcholinesterase, brain-derived neurotrophic factor, and COPS5 (Jab1) genes were upregulated, whereas Rab8 interacting protein and Rho GTPase-activating protein 4 were downregulated. These results provide important baseline genomic data for future studies aimed at investigating the long-term effects of GABA_BR activation in neurones such as their roles in neuronal growth, pathway formation and stabilization, and synaptic plasticity.

cDNA microarrays; G protein-coupled receptor; hippocampus; -aminobutyric acid