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西酞普兰可改变中风后抑郁大鼠下丘脑内细胞因子及促肾上腺皮质激素释放因子编码基因的表达。

Expression of genes encoding cytokines and corticotropin releasing factor are altered by citalopram in the hypothalamus of post-stroke depression rats.

作者信息

Wang Shan-Shan, Wang Ya-Guang, Chen Hai-Ying, Wu Zhi-Ping, Xie Heng-Ge

机构信息

Neurology Department of Nanlou Clinical Division, Chinese PLA General Hospital, Fuxing Road 28, Beijing 100853, China.

Academy of Chinese Military Medicine Science, Beijing 100850, China.

出版信息

Neuro Endocrinol Lett. 2013;34(8):773-9.

PMID:24522018
Abstract

OBJECTIVES

To establish a rat model of post-stroke depression (PSD), and examine expression of genes encoding corticotropin releasing factor (CRF), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) in the hypothalamus of PSD rats.

METHODS

Rats were subjected to middle cerebral artery occlusion (MCAO) and chronic mild unpredictable stress (CUMS). Open field test and sucrose preference were used to examine depressive-like behaviors. Observed changes in gene expression levels in the hypothalamus of PSD rats were evaluated.

RESULTS

MCAO with CUMS resulted in reduction of sucrose preference and locomotor activity. Genes encoding TNF-α, IL-1β and CRF were highly expressed in the hypothalamus of rats subjected to MCAO and CUMS. The antidepressant citalopram, a selective serotonin reuptake inhibitor, had inhibitory effects on the expression of the aforementioned genes. We observed a correlation between CRF and IL-1β mRNA levels in the citalopram-treated group of rats.

CONCLUSION

The etiology of PSD is associated with cytokine expression in the hypothalamus and with hypothalamic-pituitary-adrenal axis activity. Citalopram administration inhibited the expression of TNF-α and IL-1β transcripts in the hypothalamus, suggesting that selective serotonin reuptake inhibitors may be appropriate for PSD therapy.

摘要

目的

建立脑卒中后抑郁(PSD)大鼠模型,并检测PSD大鼠下丘脑促肾上腺皮质激素释放因子(CRF)、白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)编码基因的表达。

方法

对大鼠进行大脑中动脉闭塞(MCAO)和慢性轻度不可预测应激(CUMS)。采用旷场试验和蔗糖偏好试验检测抑郁样行为。评估PSD大鼠下丘脑基因表达水平的变化。

结果

MCAO联合CUMS导致蔗糖偏好和运动活性降低。在接受MCAO和CUMS处理的大鼠下丘脑中,TNF-α、IL-1β和CRF编码基因高表达。抗抑郁药西酞普兰,一种选择性5-羟色胺再摄取抑制剂,对上述基因的表达有抑制作用。在西酞普兰治疗的大鼠组中,我们观察到CRF和IL-1β mRNA水平之间存在相关性。

结论

PSD的病因与下丘脑细胞因子表达及下丘脑-垂体-肾上腺轴活性有关。给予西酞普兰可抑制下丘脑TNF-α和IL-1β转录本的表达,提示选择性5-羟色胺再摄取抑制剂可能适用于PSD治疗。

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