Yale University School of Medicine, Department of Psychiatry, New Haven, CT 06511, USA.
Exp Gerontol. 2011 Aug;46(8):643-59. doi: 10.1016/j.exger.2011.03.003. Epub 2011 Mar 29.
Aging in humans is associated with parallel changes in cognition, motivation, and motoric performance. Based on the human aging literature, we hypothesized that this constellation of age-related changes is mediated by the medial prefrontal cortex and that it would be observed in aging mice. Toward this end, we performed detailed assessments of cognition, motivation, and motoric behavior in aging mice. We assessed behavioral and cognitive performance in C57Bl/6 mice aged 6, 18, and 24 months, and followed this with microarray analysis of tissue from the medial prefrontal cortex and analysis of serum cytokine levels. Multivariate modeling of these data suggested that the age-related changes in cognition, motivation, motor performance, and prefrontal immune gene expression were highly correlated. Peripheral cytokine levels were also correlated with these variables, but less strongly than measures of prefrontal immune gene upregulation. To determine whether the observed immune gene expression changes were due to prefrontal microglial cells, we isolated CD11b-positive cells from the prefrontal cortex and subject them to next-generation RNA sequencing. Many of the immune changes present in whole medial prefrontal cortex were enriched in this cell population. These data suggest that, as in humans, cognition, motivation, and motoric performance in the mouse change together with age and are strongly associated with CNS immune gene upregulation.
人类衰老与认知、动机和运动表现的平行变化有关。基于人类衰老文献，我们假设这种与年龄相关的变化是由内侧前额叶皮层介导的，并且在衰老的老鼠中可以观察到。为此，我们对衰老老鼠的认知、动机和运动行为进行了详细评估。我们评估了 6、18 和 24 个月大的 C57Bl/6 小鼠的行为和认知表现，然后对内侧前额叶皮层的组织进行了微阵列分析，并分析了血清细胞因子水平。对这些数据的多变量建模表明，认知、动机、运动表现和前额叶免疫基因表达的年龄相关变化高度相关。外周细胞因子水平也与这些变量相关，但与前额叶免疫基因上调的测量相关性较弱。为了确定观察到的免疫基因表达变化是否是由于前额叶小胶质细胞引起的，我们从前额叶皮层中分离出 CD11b 阳性细胞，并对其进行下一代 RNA 测序。在整个内侧前额叶皮层中存在的许多免疫变化在该细胞群体中富集。这些数据表明，与人类一样，老鼠的认知、动机和运动表现随着年龄的增长而一起变化，并且与中枢神经系统免疫基因的上调密切相关。
