Yoshimura Yuko, Ishikawa Chihiro, Kasegai Haruki, Masuda Tomoyuki, Yoshikawa Masaaki, Shiga Takashi
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.
Neurosci Res. 2017 Feb;115:13-20. doi: 10.1016/j.neures.2016.09.008. Epub 2016 Oct 1.
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.
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。
