Eickhoff Annika, Tjaden Jonas, Stahlke Sarah, Vorgerd Matthias, Theis Verena, Matschke Veronika, Theiss Carsten
Department of Cytology, Institute of Anatomy, Ruhr-University Bochum, Bochum, Germany.
Department of Neurology, Neuromuscular Center Ruhrgebiet, University Hospital Bergmannsheil, Ruhr-Universität Bochum, Bochum, Germany.
Neural Regen Res. 2022 Nov;17(11):2465-2471. doi: 10.4103/1673-5374.339008.
Plasticity of cerebellar Purkinje cells (PC) is influenced by progesterone via the classical progesterone receptors PR-A and PR-B by stimulating dendritogenesis, spinogenesis, and synaptogenesis in these cells. Dissociated PC cultures were used to analyze progesterone effects at a molecular level on the voltage-gated T-type-Ca-channels Ca3.1, Ca3.2, and Ca3.3 as they helped determine neuronal plasticity by regulating Ca-influx in neuronal cells. The results showed direct effects of progesterone on the mRNA expression of T-type-Ca-channels, as well as on the protein kinases A and C being involved in downstream signaling pathways that play an important role in neuronal plasticity. For the mRNA expression studies of T-type-Ca-channels and protein kinases of the signaling cascade, laser microdissection and purified PC cultures of different maturation stages were used. Immunohistochemical staining was also performed to characterize the localization of T-type-Ca-channels in PC. Experimental progesterone treatment was performed on the purified PC culture for 24 and 48 hours. Our results show that progesterone increases the expression of Ca3.1 and Ca3.3 and associated protein kinases A and C in PC at the mRNA level within 48 hours after treatment at latest. These effects extend the current knowledge of the function of progesterone in the central nervous system and provide an explanatory approach for its influence on neuronal plasticity.
小脑浦肯野细胞(PC)的可塑性受孕酮影响,通过经典的孕酮受体PR-A和PR-B刺激这些细胞的树突形成、棘突形成和突触形成。使用解离的PC培养物在分子水平上分析孕酮对电压门控T型钙通道Ca3.1、Ca3.2和Ca3.3的影响,因为它们通过调节神经元细胞中的钙内流来帮助确定神经元可塑性。结果显示孕酮对T型钙通道的mRNA表达以及对参与下游信号通路的蛋白激酶A和C有直接影响,这些信号通路在神经元可塑性中起重要作用。对于T型钙通道和信号级联蛋白激酶的mRNA表达研究,使用了激光显微切割和不同成熟阶段的纯化PC培养物。还进行了免疫组织化学染色以表征PC中T型钙通道的定位。在纯化的PC培养物上进行了24小时和48小时的实验性孕酮处理。我们的结果表明,孕酮最迟在处理后48小时内,在mRNA水平上增加了PC中Ca3.1和Ca3.3以及相关蛋白激酶A和C的表达。这些效应扩展了目前关于孕酮在中枢神经系统中功能的知识,并为其对神经元可塑性的影响提供了解释途径。