Biosynthesis, mode of action, and functional significance of neurosteroids in the purkinje cell.
Biosynthesis, mode of action, and functional significance of neurosteroids in the purkinje cell.
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DOI：
10.3389/fendo.2011.00061
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发表时间：
2011
影响因子：
5.2
通讯作者：
Haraguchi S
中科院分区：
文献类型：
--
作者：
Tsutsui K;Ukena K;Sakamoto H;Okuyama S;Haraguchi S
大脑传统上被认为是外周类固醇激素的靶点。除了这个经典的概念，我们现在知道大脑有能力从胆固醇合成类固醇，即所谓的“神经类固醇”。在20世纪90年代中期，浦肯野细胞，一个重要的小脑神经元，被确定为哺乳动物和其他脊椎动物大脑中神经类固醇形成的主要部位。这一发现为理解大脑中的神经甾体生成提供了机会。此外，通过使用浦肯野细胞的研究，神经类固醇的生物学作用变得越来越清晰，浦肯野细胞是一种优秀的细胞模型，已知在记忆和学习过程中发挥重要作用。根据近十年来对哺乳动物的研究，认为浦肯野细胞在新生儿时期，当小脑神经元回路形成时，从胆固醇中主动合成孕酮和雌二醇。在发育中的浦肯野细胞中，黄体酮和雌二醇通过各自同源的核受体促进树突生长、脊髓发生和突触发生。这种由神经营养因子介导的神经类固醇作用可能有助于新生儿期小脑神经元回路的形成。孕酮代谢物3α，5α-四氢孕酮（异孕酮）也在小脑中合成，被认为是新生儿浦肯野细胞的存活因子。本文综述了目前关于浦肯野细胞发育过程中神经类固醇在小脑神经元网络突触形成中的生物合成、作用方式和功能意义的研究进展。
The brain has traditionally been considered to be a target site of peripheral steroid hormones. In addition to this classical concept, we now know that the brain has the capacity to synthesize steroids de novo from cholesterol, the so-called “neurosteroids.” In the middle 1990s, the Purkinje cell, an important cerebellar neuron, was identified as a major site for neurosteroid formation in the brain of mammals and other vertebrates. This discovery has provided the opportunity to understand neuronal neurosteroidogenesis in the brain. In addition, biological actions of neurosteroids are becoming clear by the studies using the Purkinje cell, an excellent cellular model, which is known to play an important role in memory and learning processes. Based on the studies on mammals over the past decade, it is considered that the Purkinje cell actively synthesizes progesterone and estradiol from cholesterol during neonatal life, when cerebellar neuronal circuit formation occurs. Both progesterone and estradiol promote dendritic growth, spinogenesis, and synaptogenesis via each cognate nuclear receptor in the developing Purkinje cell. Such neurosteroid actions mediated by neurotrophic factors may contribute to the formation of cerebellar neuronal circuit during neonatal life. 3α,5α-Tetrahydroprogesterone (allopregnanolone), a progesterone metabolite, is also synthesized in the cerebellum and considered to act as a survival factor of Purkinje cells in the neonate. This review summarizes the current knowledge regarding the biosynthesis, mode of action, and functional significance of neurosteroids in the Purkinje cell during development in terms of synaptic formation of cerebellar neuronal networks.