Effect of chronic citalopram on serotonin-related and stress-regulated genes in the dorsal raphe nucleus of the rat
Effect of chronic citalopram on serotonin-related and stress-regulated genes in the dorsal raphe nucleus of the rat
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DOI：
10.1016/j.euroneuro.2006.08.009
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发表时间：
2007-05-01
影响因子：
5.6
通讯作者：
Fluegge, Gabriele
中科院分区：
文献类型：
--
作者：
Abumaria, Nashat;Rygula, Rafal;Fluegge, Gabriele
采用慢性社会压力诱导抑郁样症状的抑郁模型，研究了选择性5 -羟色胺再摄取抑制剂西酞普兰（SSRI）对配对大鼠中背核基因表达的影响。色氨酸羟化酶（tryptophan hydroxylase， TPH）蛋白的表达因应激而上调，西酞普兰使其表达正常化，而TPH 1和2基因的mrna受到不同程度的影响。西酞普兰对应激动物血清素转运体mRNA无影响，但对血清素- 1a自身受体mRNA有降低作用。SSRI可抑制应激诱导的CREB结合蛋白、突触囊泡糖蛋白2b和胶质细胞N-myc下游调控基因2 mRNA的上调，但应激和非应激动物神经元特异性烯醇化酶（NSE） mRNA的上调对应激诱导的NSE蛋白上调没有影响。这些发现表明，在慢性应激大鼠中隔背核中，citatopram使TPH表达正常化，并阻断应激对神经递质释放和神经可塑性相关基因的影响。(C) 2006 Elsevier b.v.和ECPN。版权所有。
Using a model of depression in which chronic social stress induces depressive-like symptoms, we investigated effects of the selective serotonin-reuptake inhibitor (SSRI) citalopram on gene expression in the dorsal raphe nucleus of mate rats. Expression of tryptophan hydroxylase (TPH) protein was found to be upregulated by the stress and normalized by citalopram, while mRNAs for genes TPH 1 and 2 were differentially affected. Citalopram had no effect on serotonin transporter mRNA but reduced serotonin-1A autoreceptor mRNA in stressed animals. The SSRI prevented the stress-induced upregulation of mRNA for CREB binding protein, synaptic vesicle glycoprotein 2b and the glial N-myc downstream-regulated gene 2, but increased mRNA for neuron-specific enolase (NSE) in both stressed and unstressed animals having no effect on stress-induced upregulation of NSE protein. These findings demonstrate that in the dorsal raphe nucleus of chronically stressed rats, citatopram normalizes TPH expression and blocks stress effects on distinct genes related to neurotransmitter release and neuroplasticity. (C) 2006 Elsevier B. V. and ECPN. All rights reserved.