GABA减缓缺氧引起的神经营养素mRNA表达量的变化

EFFECT OF GAMA AMINOBUTYRIC ACID MODULATION ON THE ANOXIA INDUCED CHANGES OF NEUROTROPHIN mRNA LEVELS IN CULTURED HIPPOCAMPAL NEURONS

γ－氨基丁酸是中枢神经系统中的一种内源性抑制递质。近年已有实验证据揭示ＧＡＢＡ具有抵抗中枢神经元缺氧或缺血损伤的作用，但其机制尚不清楚。脑源性神经营养因子ＢＤＮＦ，神经生长因子ＮＧＦ和神经营养素－３是同一家族的成员，它们在海马脑区均有表达。为研究ＧＡＢＡ抗缺氧作用的机制，我们以培养的海马ＣＡ１神经元为材料，采用原位杂交的方法检测了缺氧后ＢＤＮＦｍＲＮＡ，ＮＧＦｍＲＮＡ和ＮＴ－３ｍＲＮＡ表达量的变化以及ＧＡＢＡ对这种变化的影响。结果显示，缺氧使ＮＧＦｍＲＮＡ和ＢＤＮＦｍＲＮＡ的表达量迅速上调且前者的变化极为剧烈，而ＮＴ－３ｍＲＮＡ的表达量显著下降；用２０μＭ的ＧＡＢＡ处理细胞后，上述缺氧引起的神经营养因子ｍＲＮＡ表达量的上升或下降幅度均被减缓，其中对ＮＧＦｍＲＮＡ表达量变化的影响最为显著。这些结果表明，ＧＡＢＡ具有稳定缺氧后ＢＤＮＦｍＲＮＡ，ＮＧＦｍＲＮＡ和ＮＴ－３ｍＲＮＡ表达水平的作用。推测这种作用与ＧＡＢＡ增加氯电导。

Gama aminobutyric acid (GABA) is a kind of inhibitory neurotransmitter in CNS. In recent years, evidences showed that GABA could protect neurons against ischemia in the brain but the detailed mechanism remained to be unclear. Brain derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin 3 (NT 3) are from the same family and are found in the hippocampus. In order to study the mechanism of GABA against anoxia, with the method of in situ hybridization, we observed the anoxia induced changes of BDNF mRNA, NGF mRNA and NT 3 mRNA in cultured hippocampal CA1 neurons and the modulatory effect of GABA on these changes. The results indicated that the expression of BDNF mRNA and NGF mRNA were upregulated and NT 3 mRNA downregulated by the anoxia. While the extent of these anoxia induced changes in mRNA was significantly attenuated in the neurons treated with 20 μM GABA.Our results suggest that during anoxia,GABA can make the expression of BDNF mRNA, NGF mRNA and NT 3 mRNA more stable. These may have the relation with the functions of GABA such as increasing CI - conductance, keeping Ca 2+ hemostasis and protection against anoxia.