Nature2014-05-21 6:17 PM

年轻血液能够抵抗小鼠年龄相关的认知性功能和突触可塑性障碍  Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice

论文摘要


随着人类寿命的增加,大部分人口遭受着年龄相关的认知损伤的困扰,因此有必要阐明一种能对抗老化影响的方法。在此我们表明,高龄动物暴露于年轻血液能够抵消和抵抗分子,结构,功能以及认知水平上大脑老化预先存在的影响。对异时联体生物的全基因组微阵列分析-在该微阵列中年轻和老年动物的循环系统被相互连接-确定了老年小鼠海马体中突触可塑性相关的转录变化。在异时联体生物的海马体中,成熟神经元树突棘密度得到增加,突触可塑性也得到了改进。从认知水平上来说,给予老年小鼠全身性年轻血浆用药改善了与年龄相关的在情境恐惧制约和空间学习和记忆方面的认知损伤。老年海马体中环磷酸腺苷反应元件结合蛋白(CREB)的激活部分调节了通过接触年轻血液引起的结构和认知改善。我们的数据表明,暴露于年轻血液的老年小鼠能够恢复突触可塑性的活力并且改善认知功能。


Abstract


As human lifespan increases, a greater fraction of the population is suffering from age-related cognitive impairments, making it important to elucidate a means to combat the effects of aging. Here we report that exposure of an aged animal to young blood can counteract and reverse pre-existing effects of brain aging at the molecular, structural, functional and cognitive level. Genome-wide microarray analysis of heterochronic parabionts—in which circulatory systems of young and aged animals are connected—identified synaptic plasticity–related transcriptional changes in the hippocampus of aged mice. Dendritic spine density of mature neurons increased and synaptic plasticity improved in the hippocampus of aged heterochronic parabionts. At the cognitive level, systemic administration of young blood plasma into aged mice improved age-related cognitive impairments in both contextual fear conditioning and spatial learning and memory. Structural and cognitive enhancements elicited by exposure to young blood are mediated, in part, by activation of the cyclic AMP response element binding protein (Creb) in the aged hippocampus. Our data indicate that exposure of aged mice to young blood late in life is capable of rejuvenating synaptic plasticity and improving cognitive function.

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