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艾司西酞普兰影响大鼠下丘脑、海马体和纹状体中的斯佩辛表达。

Escitalopram affects spexin expression in the rat hypothalamus, hippocampus and striatum.

作者信息

Pałasz Artur, Suszka-Świtek Aleksandra, Filipczyk Łukasz, Bogus Katarzyna, Rojczyk Ewa, Worthington John, Krzystanek Marek, Wiaderkiewicz Ryszard

机构信息

Department of Histology, School of Medicine in Katowice, Medical University of Silesia, Medyków 18, Katowice 40-752, Poland.

Department of Histology, School of Medicine in Katowice, Medical University of Silesia, Medyków 18, Katowice 40-752, Poland.

出版信息

Pharmacol Rep. 2016 Dec;68(6):1326-1331. doi: 10.1016/j.pharep.2016.09.002. Epub 2016 Sep 3.

Abstract

BACKGROUND

Spexin (SPX) is a recently discovered neuropeptide that exhibits a large spectrum of central and peripheral regulatory activity, especially when considered as a potent anorexigenic factor. It has already been proven that antidepressants, including selective serotonin reuptake inhibitors (SSRI), can modulate peptidergic signaling in various brain structures. Despite these findings, there is so far no information regarding the influence of treatment with the SSRI antidepressant escitalopram on brain SPX expression.

METHODS

In this current study we measured SPX mRNA and protein expression in the selected brain structures (hypothalamus, hippocampus and striatum) of rats chronically treated with a 10mg/kg dose of escitalopram using quantitative Real-Time PCR and immunohistochemistry.

RESULTS

Strikingly, long-term (4 week) drug treatment led to the downregulation of SPX expression in the rat hypothalamus. This supports the hypothesis that SPX may be involved in the hypothalamic serotonin-dependent actions of SSRI antidepressants and possibly also in the central mechanism of body mass increase. Conversely, SPX expression increased in the hippocampus and striatum.

CONCLUSIONS

This is the first report of the effects of a neuropsychiatric medication on SPX expression in animal brain. Our findings shed a new light on the pharmacology of antidepressants and may contribute to a better understanding of the alternative mechanisms responsible for antidepressant action.

摘要

背景

Spexin(SPX)是一种最近发现的神经肽,具有广泛的中枢和外周调节活性,尤其是作为一种有效的厌食因子。已经证实,包括选择性5-羟色胺再摄取抑制剂(SSRI)在内的抗抑郁药可以调节各种脑结构中的肽能信号传导。尽管有这些发现,但迄今为止,尚无关于SSRI抗抑郁药艾司西酞普兰治疗对脑SPX表达影响的信息。

方法

在本研究中,我们使用定量实时PCR和免疫组织化学方法,测量了用10mg/kg剂量的艾司西酞普兰长期治疗的大鼠所选脑结构(下丘脑、海马体和纹状体)中的SPX mRNA和蛋白表达。

结果

令人惊讶的是,长期(4周)药物治疗导致大鼠下丘脑SPX表达下调。这支持了以下假设:SPX可能参与了SSRI抗抑郁药的下丘脑5-羟色胺依赖性作用,也可能参与了体重增加的中枢机制。相反,海马体和纹状体中的SPX表达增加。

结论

这是关于神经精神药物对动物脑SPX表达影响的首次报道。我们的发现为抗抑郁药的药理学提供了新的线索,并可能有助于更好地理解抗抑郁作用的替代机制。

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