Chronic Stress and Antidepressant Agomelatine Induce Region-Specific Changes in Synapsin I Expression in the Rat Brain
Chronic Stress and Antidepressant Agomelatine Induce Region-Specific Changes in Synapsin I Expression in the Rat Brain
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DOI：
10.1002/jnr.22697
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发表时间：
2011-10-01
影响因子：
4.2
通讯作者：
Van der Zee, Eddy A.
中科院分区：
文献类型：
--
作者：
Dagyte, Girstaute;Luiten, Paul G.;Van der Zee, Eddy A.
抗抑郁药Agomelatine可作为褪黑素能受体(MT1/MT2)激动剂和5-HT2C受体拮抗剂。阿格莫拉汀已显示出治疗抑郁症的疗效，但其神经生物学效应值得进一步研究。临床前研究报道，agomelatine促进成年海马区神经发生，并增加几个神经可塑性相关分子的表达。最近，我们发现agomelatine可使海马神经元活动正常化，并促进应激损伤的大脑中的神经发生。为了进一步研究这种抗抑郁药在应激状态下的作用，我们研究了它是否会引起突触传递和可塑性调节因子--突触素I(Synl)表达的变化。成年雄性大鼠每日给予足底电击应激和阿格莫拉汀治疗3周。随后对他们的大脑进行了总的和磷酸化的Synl染色。慢性足底电击和agomelatine诱导Synl表达的区域特异性变化。虽然慢性应激增加了内侧前额叶皮质各层中Synl的总表达，但Agomelatine治疗取消了其中的一些影响。此外，慢性给予agomelatine降低了应激和非应激大鼠海马区的总Synl表达。重要的是，慢性应激降低了内侧前额叶皮质各层以及海马齿状回外层和中分子层中磷酸化Synl的比例。这些应激效应至少被阿格莫拉汀部分消除。总之，我们的数据表明，慢性应激和agomelatine治疗诱导区域特异性的Synl表达及其磷酸化的变化。此外，agomelatine部分抵消了应激对Synl的影响，表明这种抗抑郁药对突触功能有调节作用。(C)2011年Wiley-Liss，Inc.
The antidepressant agomelatine acts as a melatonergic receptor (MT1/MT2) agonist and 5-HT2C receptor antagonist. Agomelatine has demonstrated efficacy in treating depression, but its neurobiological effects merit further investigation. Preclinical studies reported that agomelatine enhances adult hippocampal neurogenesis and increases expression of several neuroplasticity-associated molecules. Recently, we showed that agomelatine normalizes hippocampal neuronal activity and promotes neurogenesis in the stress-compromised brain. To characterize further the effects of this antidepressant in the stressed brain, here we investigated whether it induces changes in the expression of synapsin I (Synl), a regulator of synaptic transmission and plasticity. Adult male rats were subjected to daily footshock stress and agomelatine treatment for 3 weeks. Their brains were subsequently stained for total and phosphorylated Synl. Chronic footshock and agomelatine induced region-specific changes in Synl expression. Whereas chronic stress increased total Synl expression in all layers of the medial prefrontal cortex, agomelatine treatment abolished some of these effects. Furthermore, chronic agomelatine administration decreased total Synl expression in the hippocampal subregions of both stressed and nonstressed rats. Importantly, chronic stress decreased the fraction of phosphorylated Synl in all layers of the medial prefrontal cortex as well as selectively in the outer and middle molecular layers of the hippocampal dentate gyrus. These stress effects were at least partially abolished by agomelatine. Altogether, our data show that chronic stress and agomelatine treatment induce region-specific changes in Synl expression and its phosphorylation. Moreover, agomelatine partially counteracts the stress effects on Synl, suggesting a modulation of synaptic function by this antidepressant. (C) 2011 Wiley-Liss, Inc.