Possible role of pineal allopregnanolone in Purkinje cell survival
Possible role of pineal allopregnanolone in Purkinje cell survival
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DOI：
10.1073/pnas.1210804109
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发表时间：
2012-12-18
影响因子：
11.1
通讯作者：
Tsutsui, Kazuyoshi
中科院分区：
文献类型：
--
作者：
Haraguchi, Shogo;Hara, Sakurako;Tsutsui, Kazuyoshi
据信，神经类固醇在大脑和其他神经系统中产生。在这里，我们表明，allopregnanolone（ALLO），一种神经类固醇，是非常产生在松果体与大脑相比，松果体ALLO作用于浦肯野细胞，一个主要的小脑神经元，以防止青少年鹌鹑的细胞凋亡。我们首先证明了松果体是神经甾体生成的主要器官。利用分子生物学技术进行的一系列实验进一步证明，幼龄鹌鹑松果体从胆固醇中重新产生多种神经甾体。重要的是，ALLO在松果体中比在大脑中更活跃地产生。松果体切除术（Px）降低了ALLO在小脑的浓度，并诱导浦肯野细胞凋亡，而管理的ALLO Px鹌鹑鸡防止浦肯野细胞凋亡。我们进一步发现，Px显着增加浦肯野细胞的数量，表达活性caspase-3，在凋亡途径中的关键蛋白酶，和每天注射ALLO的Px鹌鹑鸡减少浦肯野细胞表达活性caspase-3的数量。这些结果表明，松果体ALLO的神经保护作用与在神经元发育的早期阶段降低caspase-3活性有关。因此，我们提供的证据表明，松果体是一个重要的神经类固醇的器官，松果体ALLO可能参与浦肯野细胞的生存在发展过程中。这是松果体在发育中的小脑中形成神经元回路的重要功能。
It is believed that neurosteroids are produced in the brain and other nervous systems. Here, we show that allopregnanolone (ALLO), a neurosteroid, is exceedingly produced in the pineal gland compared with the brain and that pineal ALLO acts on the Purkinje cell, a principal cerebellar neuron, to prevent apoptosis in the juvenile quail. We first demonstrated that the pineal gland is a major organ of neurosteroidogenesis. A series of experiments using molecular and biochemical techniques has further demonstrated that the pineal gland produces a variety of neurosteroids de novo from cholesterol in the juvenile quail. Importantly, ALLO was far more actively produced in the pineal gland than in the brain. Pinealectomy (Px) decreased ALLO concentration in the cerebellum and induced apoptosis of Purkinje cells, whereas administration of ALLO to Px quail chicks prevented apoptosis of Purkinje cells. We further found that Px significantly increased the number of Purkinje cells that expressed active caspase-3, a key protease in apoptotic pathway, and daily injection of ALLO to Px quail chicks decreased the number of Purkinje cells expressing active caspase-3. These results indicate that the neuroprotective effect of pineal ALLO is associated with the decrease in caspase-3 activity during the early stage of neuronal development. We thus provide evidence that the pineal gland is an important neurosteroidogenic organ and that pineal ALLO may be involved in Purkinje cell survival during development. This is an important function of the pineal gland in the formation of neuronal circuits in the developing cerebellum.