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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >Long-term Neuroglial Cocultures as a Brain Aging Model: Hallmarks of Senescence, MicroRNA Expression Profiles, and Comparison With In Vivo Models
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Long-term Neuroglial Cocultures as a Brain Aging Model: Hallmarks of Senescence, MicroRNA Expression Profiles, and Comparison With In Vivo Models

机译:长期神经胶质细胞共培养作为一种脑衰老模型:衰老,MicroRNA表达谱和与体内模型比较的标志。

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Our purpose was to evaluate long-term neuroglial cocultures as a model for investigating senescence in the nervous system and to assess its similarities with in vivo models. To this aim, we maintained the cultures from 15 days in vitro (mature cultures) up to 27 days in vitro (senescent cultures), measuring senescence-associated, neuronal, dendritic, and astrocytic markers. Whole microRNA expression profiles were compared with those measured in the cortex of 18- and 24-month-old C57Bl/6J aged mice and of transgenic TgCRND8 mice, a model of amyloid-beta deposition. Neuroglial cocultures displayed features of cellular senescence (increased senescence-associated-beta-galactosidase activity, oxidative stress, gamma-H2AX expression, IL-6 production, astrogliosis) that were concentration dependently counteracted by the antiaging compound resveratrol (1-5 A mu M). Among the 1,080 microRNAs analyzed, 335 were downregulated or absent in 27 compared with 15 days in vitro and resveratrol reversed this effect. A substantial overlapping was found between age-associated changes in microRNA expression profiles in vitro and in TgCRND8 mice but not in physiologically aged mice, indicating that this culture model displays more similarities with pathological than physiological brain aging. Our results demonstrate that neuroglial cocultures aged in vitro can be useful for investigating the cellular and molecular mechanisms of brain aging and for preliminary testing of protective compounds.
机译:我们的目的是评估长期神经胶质细胞共培养作为研究神经系统衰老的模型,并评估其与体内模型的相似性。为此,我们从体外培养15天(成熟培养)到体外培养27天(衰老培养)维持了培养,测量了衰老相关标记,神经元标记,树突状标记和星形细胞标记。将完整的microRNA表达谱与在18和24个月大的C57Bl / 6J老年小鼠以及转基因TgCRND8小鼠(β-淀粉样蛋白沉积模型)的皮质中测得的表达谱进行了比较。神经胶质细胞共培养显示出细胞衰老的特征(衰老相关的β-半乳糖苷酶活性增加,氧化应激,γ-H2AX表达,IL-6产生,星形胶质增生),其浓度依赖性地被抗衰老化合物白藜芦醇(1-5 AμM)抵消。 )。相较于体外15天,在分析的1,080种microRNA中,有27种中的335种被下调或缺失,而白藜芦醇逆转了这种效应。发现在体外和TgCRND8小鼠中与年龄相关的microRNA表达谱变化之间存在实质性重叠,但在生理性衰老小鼠中却没有,这表明该培养模型与病理学相比生理性脑衰老显示出更多相似性。我们的结果表明,体外老化的神经胶质共培养物可用于研究脑衰老的细胞和分子机制以及保护性化合物的初步测试。

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