Martyniuk C J, Crawford A B, Hogan N S, Trudeau V L
Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, Ontario, Canada.
J Neuroendocrinol. 2005 May;17(5):269-75. doi: 10.1111/j.1365-2826.2005.01311.x.
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.
γ-氨基丁酸（GABA）是脊椎动物中枢神经系统中含量最为丰富的神经递质之一，参与诸如发育、繁殖、摄食和应激等神经内分泌过程。为了研究GABA对大脑中基因表达的影响，我们使用了一种cDNA宏阵列，该阵列包含26个参与GABA突触传递（GABA受体亚基、GABA转运体）、繁殖（促性腺激素释放激素异构体和雌激素受体α）、摄食（神经肽Y和胆囊收缩素）以及应激[促肾上腺皮质激素释放因子（CRF）]的基因。为了提高大脑中的GABA水平，我们给雌性金鱼注射了γ-乙烯基GABA（300微克/克体重）（持续24小时），γ-乙烯基GABA是一种不可逆的GABA转氨酶（GABA-T）抑制剂。我们发现，下丘脑GABA水平的升高导致GABA(A)受体β4亚基mRNA下调了2.2倍。在端脑，我们发现GABA水平的升高导致CRF mRNA增加了1.5倍，GABA(A)受体β2亚基mRNA减少了1.8倍。增加金鱼下丘脑和端脑中的GABA含量，对参与GABA合成（谷氨酸脱羧酶异构体）和降解（GABA-T）、摄食或繁殖的基因的mRNA丰度没有显著影响。我们的初步研究表明GABA对GABA受体亚基mRNA表达的调控可能是脊椎动物中一种保守的进化机制，用于调节GABA能突触传递。
