Neuropathology of mood disorders: do we see the stigmata of inflammation?
Neuropathology of mood disorders: do we see the stigmata of inflammation?
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DOI：
10.1038/tp.2016.212
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发表时间：
2016-11-08
影响因子：
6.8
通讯作者：
Savitz J
中科院分区：
文献类型：
--
作者：
Mechawar N;Savitz J
一部分情绪障碍病例的血液中炎症标志物的升高可能是由于压力，感染和/或自身免疫性导致的。但是，尚不清楚抑郁症是否是神经炎性疾病。已发现多种组织病理学和分子异常，但这些异常的病因尚不清楚。在这里，我们对该文献采取免疫学角度。在实质中报道了自杀受害者中活化的小胶质细胞或血管周围巨噬细胞的增加。相比之下，星形细胞标记通常在情绪障碍中被下调。星形细胞功能的损害可能损害谷氨酸的再摄取可能导致兴奋性毒性。炎性细胞因子和小胶质细胞/巨噬细胞衍生的喹啉酸（QA）下调了负责这种再摄取的兴奋性氨基酸转运蛋白，而质量降低的兴奋性氨基酸转运蛋白具有抑制星形胶质素合成酶的额外作用，该促谷氨酰胺合成酶转化为谷氨酸。鉴于少突胶质细胞特别容易受到炎症的影响，值得注意的是，少突胶质细胞数量或密度的减少或密度是抑郁症中最突出的发现之一。 GABA能中间神经元的结构和/或功能变化在死后脑样本中也很重要，并且可能与早期炎症性损伤有关。尽管事后数据与抑郁个体亚组的神经免疫性病因一致，但我们并不认为所有与抑郁症相关的异常都反映了神经炎症过程，甚至反映了大脑中的所有免疫学活性都是有害的。相反，我们强调了免疫信号通路在大脑功能中的普遍作用，并就当前验尸文献提供了另一种观点。
A proportion of cases with mood disorders have elevated inflammatory markers in the blood that conceivably may result from stress, infection and/or autoimmunity. However, it is not yet clear whether depression is a neuroinflammatory disease. Multiple histopathological and molecular abnormalities have been found postmortem but the etiology of these abnormalities is unknown. Here, we take an immunological perspective of this literature. Increases in activated microglia or perivascular macrophages in suicide victims have been reported in the parenchyma. In contrast, astrocytic markers generally are downregulated in mood disorders. Impairment of astrocytic function likely compromises the reuptake of glutamate potentially leading to excitotoxicity. Inflammatory cytokines and microglia/macrophage-derived quinolinic acid (QA) downregulate the excitatory amino acid transporters responsible for this reuptake, while QA has the additional effect of inhibiting astroglial glutamine synthetase, which converts glutamate to glutamine. Given that oligodendroglia are particularly vulnerable to inflammation, it is noteworthy that reductions in numbers or density of oligodendrocyte cells are one of the most prominent findings in depression. Structural and/or functional changes to GABAergic interneurons also are salient in postmortem brain samples, and may conceivably be related to early inflammatory insults. Although the postmortem data are consistent with a neuroimmune etiology in a subgroup of depressed individuals, we do not argue that all depression-associated abnormalities are reflective of a neuroinflammatory process or even that all immunological activity in the brain is deleterious. Rather, we highlight the pervasive role of immune signaling pathways in brain function and provide an alternative perspective on the current postmortem literature.