Department of Neurobiology and Anatomy and Center for Visual Science, University of Rochester, Rochester, New York 14642, USA.
Glia. 2012 Apr;60(4):541-58. doi: 10.1002/glia.22287. Epub 2012 Jan 5.
Normal aging is often accompanied by a progressive loss of receptor sensitivity in hearing and vision, whose consequences on cellular function in cortical sensory areas have remained largely unknown. By examining the primary auditory (A1) and visual (V1) cortices in two inbred strains of mice undergoing either age-related loss of audition (C57BL/6J) or vision (CBA/CaJ), we were able to describe cellular and subcellular changes that were associated with normal aging (occurring in A1 and V1 of both strains) or specifically with age-related sensory loss (only in A1 of C57BL/6J or V1 of CBA/CaJ), using immunocytochemical electron microscopy and light microscopy. While the changes were subtle in neurons, glial cells and especially microglia were transformed in aged animals. Microglia became more numerous and irregularly distributed, displayed more variable cell body and process morphologies, occupied smaller territories, and accumulated phagocytic inclusions that often displayed ultrastructural features of synaptic elements. Additionally, evidence of myelination defects were observed, and aged oligodendrocytes became more numerous and were more often encountered in contiguous pairs. Most of these effects were profoundly exacerbated by age-related sensory loss. Together, our results suggest that the age-related alteration of glial cells in sensory cortical areas can be accelerated by activity-driven central mechanisms that result from an age-related loss of peripheral sensitivity. In light of our observations, these age-related changes in sensory function should be considered when investigating cellular, cortical, and behavioral functions throughout the lifespan in these commonly used C57BL/6J and CBA/CaJ mouse models.
正常衰老通常伴随着听觉和视觉受体敏感性的逐渐丧失,但其对皮质感觉区域细胞功能的影响在很大程度上仍不清楚。通过检查两种近交系小鼠(C57BL/6J 和 CBA/CaJ)中与年龄相关的听觉丧失(C57BL/6J)或视觉丧失(CBA/CaJ)相关的初级听觉(A1)和视觉(V1)皮质,我们能够描述与正常衰老相关的细胞和亚细胞变化(发生在两种品系的 A1 和 V1 中)或与年龄相关的感觉丧失特异性相关的变化(仅在 C57BL/6J 的 A1 或 CBA/CaJ 的 V1 中),使用免疫细胞化学电子显微镜和光镜。虽然神经元的变化很细微,但神经胶质细胞,特别是小胶质细胞在老年动物中发生了变化。小胶质细胞变得更多,分布不规则,显示出更多变化的细胞体和突起形态,占据更小的区域,并积累吞噬体,这些吞噬体通常显示突触元件的超微结构特征。此外,还观察到髓鞘缺陷的证据,老年少突胶质细胞变得更多,并且更常在连续对中遇到。这些影响中的大多数都被与年龄相关的感觉丧失严重加剧。总之,我们的研究结果表明,感觉皮质区域胶质细胞的年龄相关改变可以通过源自外周敏感性丧失的活性驱动的中枢机制加速。鉴于我们的观察结果,在这些常用的 C57BL/6J 和 CBA/CaJ 小鼠模型中,在整个生命周期中研究细胞、皮质和行为功能时,应该考虑到这些与年龄相关的感觉功能变化。