脑内别孕烯醇酮在大鼠孕期及产后大脑中γ-氨基丁酸A型受体可塑性中的作用
Role of brain allopregnanolone in the plasticity of gamma-aminobutyric acid type A receptor in rat brain during pregnancy and after delivery.
作者信息
Concas A, Mostallino M C, Porcu P, Follesa P, Barbaccia M L, Trabucchi M, Purdy R H, Grisenti P, Biggio G
机构信息
Department of Experimental Biology, University of Cagliari, 09123 Cagliari, Italy.
出版信息
Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13284-9. doi: 10.1073/pnas.95.22.13284.
The relation between changes in brain and plasma concentrations of neurosteroids and the function and structure of gamma-aminobutyric acid type A (GABAA) receptors in the brain during pregnancy and after delivery was investigated in rats. In contrast with plasma, where all steroids increased in parallel, the kinetics of changes in the cerebrocortical concentrations of progesterone, allopregnanolone (AP), and allotetrahydrodeoxycorticosterone (THDOC) diverged during pregnancy. Progesterone was already maximally increased between days 10 and 15, whereas AP and allotetrahydrodeoxycorticosterone peaked around day 19. The stimulatory effect of muscimol on 36Cl- uptake by cerebrocortical membrane vesicles was decreased on days 15 and 19 of pregnancy and increased 2 days after delivery. Moreover, the expression in cerebral cortex and hippocampus of the mRNA encoding for gamma2L GABAA receptor subunit decreased during pregnancy and had returned to control values 2 days after delivery. Also alpha1, alpha2, alpha3, alpha4, beta1, beta2, beta3, and gamma2S mRNAs were measured and failed to change during pregnancy. Subchronic administration of finasteride, a 5alpha-reductase inhibitor, to pregnant rats reduced the concentrations of AP more in brain than in plasma as well as prevented the decreases in both the stimulatory effect of muscimol on 36Cl- uptake and the decrease of gamma2L mRNA observed during pregnancy. These results indicate that the plasticity of GABAA receptors during pregnancy and after delivery is functionally related to fluctuations in endogenous brain concentrations of AP whose rate of synthesis/metabolism appears to differ in the brain, compared with plasma, in pregnant rats.
在大鼠中研究了孕期及产后大脑和血浆中神经甾体浓度变化与大脑中γ-氨基丁酸A型（GABAA）受体功能和结构之间的关系。与血浆中所有甾体平行增加不同，孕期大脑皮质中孕酮、别孕烯醇酮（AP）和别四氢脱氧皮质酮（THDOC）浓度变化的动力学有所不同。孕酮在第10至15天已达到最大增加，而AP和别四氢脱氧皮质酮在第19天左右达到峰值。孕期第15天和第19天，蝇蕈醇对大脑皮质膜囊泡摄取36Cl-的刺激作用降低，产后2天增加。此外，孕期大脑皮质和海马中编码γ2L GABAA受体亚基的mRNA表达降低，产后2天恢复到对照值。还检测了α1、α2、α3、α4、β1、β2、β3和γ2S mRNA，孕期未发生变化。对怀孕大鼠亚慢性给予5α-还原酶抑制剂非那雄胺，大脑中AP浓度的降低比血浆中更明显，同时也防止了孕期观察到的蝇蕈醇对36Cl-摄取刺激作用的降低以及γ2L mRNA的减少。这些结果表明，孕期及产后GABAA受体的可塑性在功能上与内源性大脑AP浓度的波动有关，在怀孕大鼠中，其合成/代谢速率在大脑中与血浆中似乎有所不同。
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