Profile of changes in gene expression in cultured hippocampal neurones evoked by the GABAB receptor agonist baclofen.
Metabotropic gamma-aminobutyric acid receptors (GABA(B)Rs) 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(B)Rs by baclofen but are not changed by baclofen in the presence of the GABA(B)R 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(B)R activation in neurones such as their roles in neuronal growth, pathway formation and stabilization, and synaptic plasticity.
Ghorbel
Mohamed T
MT
Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University of Bristol, Bristol, United Kingdom.
Becker
Kevin G
KG
Henley
Jeremy M
JM
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004705:Endocytosis / Q000235:genetics; D058786:GABA-B Receptor Agonists; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D058786:GABA-B Receptor Agonists; D047908:Intracellular Signaling Peptides and Proteins; D018080:Receptors, GABA-B; D001418:Baclofen