Submitted on September 7, 2004
Accepted on March 18, 2005
Profile of changes in gene expression in cultured hippocampal neurones evoked by the GABAB receptor agonist baclofen
Mohamed T Ghorbel1, Kevin G Becker2, and Jeremy M Henley1*
1 MRC Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University of Bristol, Bristol, United Kingdom
2 GRC, National Institute on Ageing, NIH, Baltimore, MD, USA
* To whom correspondence should be addressed. E-mail: j.m.henley{at}bris.ac.uk.
Metabotropic 
-aminobutyric acid receptors (GABABRs) 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 down-regulated by activation of GABABRs by baclofen but are not changed by baclofen in the presence of the GABABR CGP55845A. Our data show for the first time regulation of transcription of defined mRNAs following specific GABAB receptor activation. The identified genes can be grouped into those encoding signal transduction, endocytosis/trafficking and structural classes of proteins. For example, butyrylcholinesterase (BuChE), brain-derived neurotrophic factor (BDNF) and COPS5 (Jab1) genes were up-regulated whereas Rab8 interacting protein and Rho GTPase activating protein 4 (ARHGAP4) were down-regulated. These results provide important baseline genomic data for future studies aimed at investigating the long-term effects of GABABR activation in neurones such as their roles in neuronal growth, pathway formation and stabilisation and synaptic plasticity.
