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普通狨猴中tau蛋白过度磷酸化和营养不良性小胶质细胞的证据。

Evidence of Tau Hyperphosphorylation and Dystrophic Microglia in the Common Marmoset.

作者信息

Rodriguez-Callejas Juan D, Fuchs Eberhard, Perez-Cruz Claudia

机构信息

Laboratory of Neuroplasticity and Neurodegeneration, Department of Pharmacology, Center for Research and Advanced Studies (CINVESTAV) Mexico City, Mexico.

Clinical Neurobiology Laboratory, German Primate Center - Leibniz Institute for Primate Research, Göttingen Germany.

出版信息

Front Aging Neurosci. 2016 Dec 22;8:315. doi: 10.3389/fnagi.2016.00315. eCollection 2016.

Abstract

Common marmosets () have recently gained popularity in biomedical research as models of aging research. Basically, they confer advantages from other non-human primates due to their shorter lifespan with onset of appearance of aging at 8 years. Old marmosets present some markers linked to neurodegeneration in the brain such as amyloid beta (Aβ) and Aβ. However, there are no studies exploring other cellular markers associated with neurodegenerative diseases in this non-human primate. Using immunohistochemistry, we analyzed brains of male adolescent, adult, old, and aged marmosets. We observed accumulation of Aβ and Aβ in the cortex of aged subjects. Tau hyperphosphorylation was already detected in the brain of adolescent animals and increased with aging in a more fibrillary form. Microglia activation was also observed in the aging process, while a dystrophic phenotype accumulates in aged subjects. Interestingly, dystrophic microglia contained hyperphosphorylated tau, but active microglia did not. These results support previous findings regarding microglia dysfunctionality in aging and neurodegenerative diseases as Alzheimer's disease. Further studies should explore the functional consequences of these findings to position this non-human primate as animal model of aging and neurodegeneration.

摘要

普通狨猴()最近作为衰老研究模型在生物医学研究中受到欢迎。基本上,由于它们寿命较短,8岁时就开始出现衰老迹象,这使它们相对于其他非人类灵长类动物具有优势。老年狨猴呈现出一些与大脑神经退行性变相关的标志物,如β淀粉样蛋白(Aβ)和Aβ。然而,尚无研究探索这种非人类灵长类动物中与神经退行性疾病相关的其他细胞标志物。我们使用免疫组织化学方法分析了雄性青少年、成年、老年和高龄狨猴的大脑。我们观察到高龄受试者大脑皮层中Aβ和Aβ的积累。在青少年动物的大脑中已经检测到tau蛋白过度磷酸化,并且随着年龄增长以更纤维化的形式增加。在衰老过程中还观察到小胶质细胞激活,而在高龄受试者中出现营养不良性表型积累。有趣的是,营养不良性小胶质细胞含有过度磷酸化的tau蛋白,但活跃的小胶质细胞则没有。这些结果支持了先前关于衰老和神经退行性疾病(如阿尔茨海默病)中小胶质细胞功能障碍性的研究发现。进一步的研究应探索这些发现的功能后果,以便将这种非人类灵长类动物定位为衰老和神经退行性变的动物模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2e5/5177639/b55dde38e28c/fnagi-08-00315-g001.jpg

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