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4'-氯地西泮以性别依赖的方式调节原代海马神经元的发育。

4'-Chlorodiazepam modulates the development of primary hippocampal neurons in a sex-dependent manner.

作者信息

Arbo B D, Vieira-Marques C, Ruiz-Palmero I, Ortiz-Rodriguez A, Arevalo M A, Garcia-Segura L M, Ribeiro M F

机构信息

Laboratório de Interação Neuro-Humoral, Department of Physiology, ICBS - Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite, 500 (90050-170), Porto Alegre, RS, Brazil; Instituto Cajal, CSIC, Avenida Doctor Arce, 37 (28002), Madrid, Spain.

Laboratório de Interação Neuro-Humoral, Department of Physiology, ICBS - Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite, 500 (90050-170), Porto Alegre, RS, Brazil; Instituto Cajal, CSIC, Avenida Doctor Arce, 37 (28002), Madrid, Spain.

出版信息

Neurosci Lett. 2017 Feb 3;639:98-102. doi: 10.1016/j.neulet.2016.12.067. Epub 2016 Dec 29.

DOI:10.1016/j.neulet.2016.12.067
PMID:28041963
Abstract

The translocator protein 18kDa (TSPO) is located in the outer mitochondrial membrane and is involved in the cholesterol transport into the mitochondria and in the regulation of steroidogenesis and other mitochondrial functions. It is known that steroid hormones, such as estradiol, testosterone and dihydrotestosterone are neuroprotective and regulate neuritogenesis in the CNS by different mechanisms. However, the developmental effects of TSPO ligands in the CNS are not known. Therefore, the aim of this study was to identify the developmental effects of 4'-chlorodiazepam (4'-CD), a TSPO ligand, in primary cultures of male and female mouse hippocampal neurons. We observed that female neurons showed an advanced neuritogenesis compared to male neurons after 2days in vitro. Moreover, it was shown that 4'-CD administration accelerated the maturation of male hippocampal neurons, without changing the development of female neurons. These findings, showing that 4'-CD modulates the development of hippocampal neurons in a sex-dependent manner, suggest that TSPO may be involved in the regulation of neuritogenesis.

摘要

转位蛋白18千道尔顿(TSPO)位于线粒体外膜,参与胆固醇转运进入线粒体以及甾体激素生成和其他线粒体功能的调节。已知甾体激素,如雌二醇、睾酮和二氢睾酮具有神经保护作用,并通过不同机制调节中枢神经系统中的神经突生长。然而,TSPO配体在中枢神经系统中的发育影响尚不清楚。因此,本研究的目的是确定TSPO配体4'-氯地西泮(4'-CD)对雄性和雌性小鼠海马神经元原代培养物的发育影响。我们观察到,体外培养2天后,雌性神经元的神经突生长比雄性神经元更超前。此外,研究表明,给予4'-CD可加速雄性海马神经元的成熟,而不改变雌性神经元的发育。这些结果表明4'-CD以性别依赖的方式调节海马神经元的发育,提示TSPO可能参与神经突生长的调节。

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