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左旋多巴诱导的抑郁模型在雄性和雌性中表现出负趋地性缺陷和差异基因表达。

The Levodopa-Induced Depression Model Exhibits Negative Geotaxis Deficits and Differential Gene Expression in Males and Females.

作者信息

Moulin Thiago C, Ferro Federico, Hoyer Angela, Cheung Pierre, Williams Michael J, Schiöth Helgi B

机构信息

Functional Pharmacology Unit, Department of Neuroscience, Uppsala University, Uppsala, Sweden.

Institute for Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow, Russia.

出版信息

Front Neurosci. 2021 May 17;15:653470. doi: 10.3389/fnins.2021.653470. eCollection 2021.

Abstract

More than 320 million people live with depression in the world, a disorder that severely limits psychosocial functioning and diminishes quality of life. The prevalence of major depression is almost two times higher in women than in men. However, the molecular mechanisms of its sex-specific pathophysiology are still poorly understood. is an established model for neurobiological research of depression-like states, as well as for the study of molecular and genetic sex differences in the brain. Here, we investigated sex-specific effects on forced-climbing locomotion (negative geotaxis) and gene expression of a fly model of depression-like phenotypes induced by levodopa administration, which was previously shown to impair normal food intake, mating frequency, and serotonin concentration. We observed that both males and females show deficits in the forced-climbing paradigm; however, modulated by distinct gene expression patterns after levodopa administration. Our results suggest that models can be a valuable tool for identifying the molecular mechanisms underlying the difference of depressive disorder prevalence between men and women.

摘要

全球有超过3.2亿人患有抑郁症,这种疾病严重限制心理社会功能并降低生活质量。重度抑郁症的患病率女性几乎是男性的两倍。然而,其性别特异性病理生理学的分子机制仍知之甚少。果蝇是抑郁症样状态神经生物学研究以及大脑分子和遗传性别差异研究的既定模型。在这里,我们研究了左旋多巴给药诱导的抑郁症样表型果蝇模型对强迫攀爬运动(负趋地性)和基因表达的性别特异性影响,左旋多巴给药先前已被证明会损害正常食物摄入、交配频率和血清素浓度。我们观察到,雄性和雌性在强迫攀爬范式中均表现出缺陷;然而,左旋多巴给药后由不同的基因表达模式调节。我们的结果表明,果蝇模型可成为识别男女抑郁症患病率差异背后分子机制的宝贵工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5699/8165388/488baeb739bc/fnins-15-653470-g001.jpg

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