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5-羟色胺受体在发育中小鼠皮质神经元中α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体及脑源性神经营养因子表达中的作用

Roles of 5-HT receptor in the expression of AMPA receptor and BDNF in developing mouse cortical neurons.

作者信息

Yoshimura Yuko, Ishikawa Chihiro, Kasegai Haruki, Masuda Tomoyuki, Yoshikawa Masaaki, Shiga Takashi

机构信息

Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.

Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan; Department of Neurobiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.

出版信息

Neurosci Res. 2017 Feb;115:13-20. doi: 10.1016/j.neures.2016.09.008. Epub 2016 Oct 1.

Abstract

The possible interactions between serotonergic and glutamatergic systems during neural development and under the pathogenesis of depression remain unclear. We now investigated roles of 5-HT receptor in the mRNA expression of AMPA receptor subunits (GluR1 and GluR2) and brain-derived neurotrophic factor (BDNF) using primary culture of cerebral cortex of mouse embryos. Neurons at embryonic day 18 were cultured for 3days or 14days and then treated with 5-HT receptor agonist (8-OH-DPAT) for 3h or 24h. In neurons cultured for 3 days, 8-OH-DPAT treatment for both 3h and 24h increased the mRNA levels of BDNF and GluR1, but not GluR2. In neurons cultured for 14 days, however, 8-OH-DPAT had no effects on these mRNA levels. Next, we examined in vivo roles of 5-HT receptor by administration of 8-OH-DPAT to newborn mice. Twenty-four hours after the oral administration of 8-OH-DPAT, the mRNA expression of BDNF was decreased in the frontal cortex, but had no effects on the mRNA expression of GluR1 and GluR2. Taken together, the present study suggests that 5-HT receptor activation modulates mRNA expression of AMPA receptor subunit and BDNF in cortical neurons, and the effects are different between in vitro and in vivo.

摘要

在神经发育过程以及抑郁症发病机制中,血清素能系统和谷氨酸能系统之间可能存在的相互作用仍不清楚。我们现在利用小鼠胚胎大脑皮层的原代培养物,研究了5-羟色胺(5-HT)受体在α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体亚基(GluR1和GluR2)以及脑源性神经营养因子(BDNF)的信使核糖核酸(mRNA)表达中的作用。将胚胎第18天的神经元培养3天或14天,然后用5-HT受体激动剂(8-羟基-二丙基氨基四氢吡啶,8-OH-DPAT)处理3小时或24小时。在培养3天的神经元中,8-OH-DPAT处理3小时和24小时均增加了BDNF和GluR1的mRNA水平,但未增加GluR2的mRNA水平。然而,在培养14天的神经元中,8-OH-DPAT对这些mRNA水平没有影响。接下来,我们通过给新生小鼠施用8-OH-DPAT来研究5-HT受体在体内的作用。口服8-OH-DPAT 24小时后,额叶皮层中BDNF的mRNA表达降低,但对GluR1和GluR2的mRNA表达没有影响。综上所述,本研究表明5-HT受体激活可调节皮层神经元中AMPA受体亚基和BDNF的mRNA表达,且体外和体内的作用有所不同。

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