Brain and Mind Research Institute, University of Sydney, Camperdown, New South Wales, Australia.
Int Psychogeriatr. 2012 Dec;24(12):1878-90. doi: 10.1017/S1041610212000828. Epub 2012 Jul 3.
Late-life depression (LLD) has a complex and multifactoral etiology. There is growing interest in elucidating how glia, acting alone or as part of a glial-neuronal network, may contribute to the pathophysiology of depression. In this paper, we explore results from neuroimaging studies showing gray-matter volume loss in key frontal and subcortical structures implicated in LLD, and present the few histological studies that have examined neuronal and glial densities in these regions. Compared to results in younger people with depression, there appear to be age-dependent differences in neuronal pathology but the changes in glial pathology may be more subtle, perhaps reflecting a longer-term compensatory gliosis to earlier damage. We then consider the mechanisms by which both astrocytes and microglia may mediate and modulate neuronal dysfunction and possible degeneration in depression. These include a critical role in the response to peripheral inflammation and central microglial activation, as well as a key role in glutamate metabolism. Advances in our understanding of glia are highlighted, including the role of microglia as "electricians" of the brain and astrocytes as key communicating cells, an integral part of the tripartite synapse. Finally, implications for clinicians are discussed, including the consideration of glia as biomarkers for LLD and incorporation of glia into future therapeutic strategies.
老年期抑郁症（LLD）的病因复杂且具有多因素性。目前，人们越来越关注阐明胶质细胞（单独或作为胶质-神经元网络的一部分）如何促成抑郁症的病理生理学。本文探讨了神经影像学研究的结果，这些研究显示了与 LLD 相关的关键额前和皮质下结构的灰质体积损失，并介绍了少数研究这些区域神经元和神经胶质密度的组织学研究。与年轻抑郁症患者的结果相比，神经元病理学似乎存在年龄依赖性差异，但神经胶质病理学的变化可能更为微妙，可能反映了对早期损伤的长期代偿性神经胶质增生。然后，我们考虑了星形胶质细胞和小胶质细胞可能介导和调节抑郁症中神经元功能障碍和可能的退行性变的机制。这些机制包括在对外周炎症和中枢小胶质细胞激活的反应中起关键作用，以及在谷氨酸代谢中的关键作用。本文强调了对神经胶质的理解的进展，包括小胶质细胞作为大脑的“电工”以及星形胶质细胞作为关键的通讯细胞在三突触中的重要作用。最后，讨论了对临床医生的影响，包括将神经胶质作为 LLD 的生物标志物的考虑以及将神经胶质纳入未来的治疗策略。
