GABAergic Modulation of the Expression of Genes Involved in GABA Synaptic Transmission and Stress in the Hypothalamus and Telencephalon of the Female Goldfish (Carassius auratus)

Abstract

GABA is one of the most abundant neurotransmitters in the vertebrate central nervous system and is involved in neuroendocrine processes such as development, reproduction, feeding and stress. To examine the effect of GABA on gene expression in the brain, we used a cDNA macroarray containing 26 genes involved in GABA synaptic transmission (GABA receptor subunits, GABA transporters), reproduction (gonadotrophin-releasing hormone isoforms and oestrogen receptor alpha), feeding (neuropeptide Y and cholecystokinin), and stress [corticotrophin-releasing factor (CRF)]. To elevate GABA levels in the brain, we injected female goldfish with gamma-vinyl GABA (300 microg/g of body weight) (24 h), an irreversible inhibitor of the enzyme GABA transaminase (GABA-T). We found that increased levels of GABA in the hypothalamus resulted in a 2.2-fold down-regulation of GABA(A) receptor beta4 subunit mRNA. In the telencephalon, we found that increased GABA levels resulted in a 1.5-fold increase of CRF mRNA and a 1.8-fold decrease of GABA(A) receptor beta2 subunit mRNA. Increasing GABA in the hypothalamus and telencephalon of the goldfish did not significantly affect the mRNA abundance of genes involved in GABA synthesis (glutamic acid decarboxylase isoforms) and degradation (GABA-T), feeding, or reproduction. Our preliminary study suggests that the regulation of GABA receptor subunit mRNA expression by GABA may be a conserved evolutionary mechanism in vertebrates to modulate GABAergic synaptic transmission.