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小鼠束缚慢性应激模型中海马基因表达的生物标志物

Biomarkers of hippocampal gene expression in a mouse restraint chronic stress model.

作者信息

Ubaldi Massimo, Ricciardelli Eugenia, Pasqualini Lorenza, Sannino Giuseppina, Soverchia Laura, Ruggeri Barbara, Falcinelli Silvia, Renzi Alessandra, Ludka Colleen, Ciccocioppo Roberto, Hardiman Gary

机构信息

School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri 9, Camerino, Italy.

出版信息

Pharmacogenomics. 2015;16(5):471-82. doi: 10.2217/pgs.15.3.

Abstract

OBJECTIVE

Acute stress provides many beneficial effects whereas chronic stress contributes to a variety of human health issues including anxiety, depression, gastrointestinal problems, cardiac disease, sleep disorders and obesity. The goal of this work was to identify, using a rodent model, hippocampal gene signatures associated with prolonged chronic stress representing candidate biomarkers and therapeutic targets for early diagnosis and pharmacological intervention for stress induced disease.

MATERIALS & METHODS: Mice underwent 'restraint stress' over 7 consecutive days and hippocampal gene-expression changes were analyzed at 3, 12 and 24 h following the final restraint treatment.

RESULTS

Data indicated that mice exposed to chronic restraint stress exhibit a differential gene-expression profile compared with non-stressed controls. The greatest differences were observed 12 and 24 h following the final stress test.

CONCLUSION

Our study indicated that Gpr88, Ttr, Gh and Tac1 mRNAs were modulated in mice exposed to chronic restraint stress. These transcripts represent a panel of biomarkers and druggable targets for further analysis in the context of chronic stress associated disease in humans.

摘要

目的

急性应激具有诸多有益影响,而慢性应激则会引发包括焦虑、抑郁、胃肠道问题、心脏病、睡眠障碍和肥胖在内的多种人类健康问题。本研究的目的是利用啮齿动物模型,识别与长期慢性应激相关的海马基因特征,这些特征可作为候选生物标志物和治疗靶点,用于应激诱导疾病的早期诊断和药物干预。

材料与方法

小鼠连续7天接受“束缚应激”,并在最后一次束缚处理后的3、12和24小时分析海马基因表达变化。

结果

数据表明,与未受应激的对照组相比,暴露于慢性束缚应激的小鼠呈现出不同的基因表达谱。在最后一次应激测试后的12和24小时观察到最大差异。

结论

我们的研究表明,在暴露于慢性束缚应激的小鼠中,Gpr88、Ttr、Gh和Tac1 mRNA受到调控。这些转录本代表了一组生物标志物和可成药靶点,可在人类慢性应激相关疾病的背景下进行进一步分析。

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