Centre de Recherche, Centre Hospitalier Universitaire (CHU) Sainte-Justine, Département de Pédiatrie, Université de Montréal, 3175 Chem. de La Côte-Sainte-Catherine, Montreal, QC, H3T 1C5, Canada.
Département de Neurosciences, Université de Montréal, 2900, Boul. Édouard-Montpetit, Montreal, QC, H3T 1J4, Canada.
Sci Rep. 2022 Feb 24;12(1):3186. doi: 10.1038/s41598-022-06769-5.
Sexual differentiation of the brain is influenced by testosterone and its metabolites during the perinatal period, when many aspects of brain development, including the maturation of GABAergic transmission, occur. Whether and how testosterone signaling during the perinatal period affects GABAergic transmission is unclear. Here, we analyzed GABAergic circuit functional markers in male, female, testosterone-treated female, and testosterone-insensitive male rats after the first postnatal week and in young adults. In the hippocampus, mRNA levels of proteins associated with GABA signaling were not significantly affected at postnatal day (P) 7 or P40. Conversely, membrane protein levels of KCC2, which are critical for determining inhibition strength, were significantly higher in females compared to males and testosterone-treated females at P7. Further, female and testosterone-insensitive male rats at P7 showed higher levels of the neurotrophin BDNF, which is a powerful regulator of neuronal function, including GABAergic transmission. Finally, spontaneous GABAergic currents in hippocampal CA1 pyramidal cells were more frequent in females and testosterone-insensitive males at P40. Overall, these results show that perinatal testosterone levels modulate GABAergic circuit function, suggesting a critical role of perinatal sex hormones in regulating network excitability in the adult hippocampus.
大脑的性别分化受围产期睾酮及其代谢物的影响，在此期间，大脑的许多方面都在发育，包括 GABA 能传递的成熟。围产期的睾酮信号是否以及如何影响 GABA 能传递尚不清楚。在这里，我们分析了雄性、雌性、经睾酮处理的雌性和雄性大鼠在出生后第一周以及在年轻成年期的 GABA 能回路功能标志物。在海马体中，与 GABA 信号相关的蛋白的 mRNA 水平在出生后第 7 天或第 40 天没有明显变化。相反，KCC2 的膜蛋白水平在雌性大鼠中明显高于雄性和经睾酮处理的雌性大鼠，而 KCC2 对确定抑制强度至关重要。此外，出生后第 7 天的雌性和雄性大鼠的神经营养因子 BDNF 水平也较高，BDNF 是调节神经元功能（包括 GABA 能传递）的强大调节剂。最后，在出生后第 40 天，海马 CA1 锥体神经元中的自发性 GABA 能电流在雌性和雄性大鼠中更为频繁。总的来说，这些结果表明围产期的睾酮水平调节 GABA 能回路功能，提示围产期性激素在调节成年海马体网络兴奋性方面起着关键作用。
