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衰老以性别二态性模式改变斑马鱼(Danio rerio)突触的分子动力学。

Aging alters the molecular dynamics of synapses in a sexually dimorphic pattern in zebrafish (Danio rerio).

作者信息

Karoglu Elif Tugce, Halim Dilara Ozge, Erkaya Bahriye, Altaytas Ferda, Arslan-Ergul Ayca, Konu Ozlen, Adams Michelle M

机构信息

Interdisciplinary Graduate Program in Neuroscience, Aysel Sabuncu Brain Research Center, Bilkent University, Ankara, Turkey; UNAM-Institute of Materials Science and Nanotechnology, Bilkent University, Ankara, Turkey; Department of Molecular Biology and Genetics Zebrafish Facility, Bilkent University, Ankara, Turkey.

Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey.

出版信息

Neurobiol Aging. 2017 Jun;54:10-21. doi: 10.1016/j.neurobiolaging.2017.02.007. Epub 2017 Feb 20.

DOI:10.1016/j.neurobiolaging.2017.02.007
PMID:28314159
Abstract

The zebrafish has become a popular model for studying normal brain aging due to its large fecundity, conserved genome, and available genetic tools; but little data exists about neurobiological age-related alterations. The current study tested the hypothesis of an association between brain aging and synaptic protein loss across males and females. Western blot analysis of synaptophysin (SYP), a presynaptic vesicle protein, and postsynaptic density-95 (PSD-95) and gephyrin (GEP), excitatory and inhibitory postsynaptic receptor-clustering proteins, respectively, was performed in young, middle-aged, and old male and female zebrafish (Danio rerio) brains. Univariate and multivariate analyses demonstrated that PSD-95 significantly increased in aged females and SYP significantly decreased in males, but GEP was stable. Thus, these key synaptic proteins vary across age in a sexually dimorphic manner, which has been observed in other species, and these consequences may represent selective vulnerabilities for aged males and females. These data expand our knowledge of normal aging in zebrafish, as well as further establish this model as an appropriate one for examining human brain aging.

摘要

由于斑马鱼繁殖力强、基因组保守且有可用的遗传工具,它已成为研究正常脑衰老的常用模型;但关于神经生物学年龄相关变化的数据却很少。当前研究检验了脑衰老与雄性和雌性突触蛋白损失之间存在关联的假设。分别对年轻、中年和老年雄性和雌性斑马鱼(Danio rerio)脑内的突触小泡蛋白突触素(SYP)、兴奋性和抑制性突触后受体聚集蛋白突触后致密蛋白95(PSD - 95)和桥连蛋白(GEP)进行了蛋白质免疫印迹分析。单变量和多变量分析表明,PSD - 95在老年雌性中显著增加,SYP在雄性中显著减少,但GEP保持稳定。因此,这些关键突触蛋白在年龄上呈现出性别二态性变化,这在其他物种中也有观察到,这些结果可能代表了老年雄性和雌性的选择性脆弱性。这些数据扩展了我们对斑马鱼正常衰老的认识,并进一步将该模型确立为研究人类脑衰老的合适模型。

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