Microglial activation is a component of neurodegenerative pathology. Here, we examine whether activated microglia participate in age-related dopaminergic (DA) cell death in the substantia nigra pars compacta (SNc) of the zitter (zi/zi) rat, a mutant characterized by deletion of the attractin gene. Confocal microscopy with double-immunohistochemical staining revealed activated microglia-formed cell-clusters surrounding DA neurons in the SNc from 2 weeks after birth. An immunoelectron microscopic study showed that the cytoplasm of activated microglia usually contains phagosome-like vacuoles and lamellar inclusions. Expression levels of the pro-inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) were increased in the midbrain of 2-month-old zi/zi rats. Chronic treatment with the anti-inflammatory agent minocycline altered the morphology of the microglia, reduced cluster formation by the microglia, and attenuated DA cell death in the SNc, and reduced the expression of IL-1β in the midbrain. These results indicate that activated microglia, at least in part and especially at the initial phase, contribute to DA cell death in the SNc of the zi/zi rat.

小胶质细胞激活是神经退行性病变的一个组成部分。在这里，我们检查了激活的小胶质细胞是否参与了以Zitter（zi / zi）大鼠为特征的黑质致密部致密部（SNc）的年龄相关的多巴胺能（DA）细胞死亡，该突变体的特征是吸引素基因的缺失。共免疫双免疫组化显微镜检查显示，出生后两周后，SNc中DA神经元周围有活化的小胶质细胞形成的细胞团。免疫电子显微镜研究表明，活化的小胶质细胞质通常包含吞噬样液泡和层状内含物。促炎细胞因子白介素-1β（IL-1β），肿瘤坏死因子-α（TNF-α）的表达水平）和诱导型一氧化氮合酶（iNOS）在2个月大的zi / zi大鼠的中脑中增加。用抗炎药米诺环素进行的慢性治疗改变了小胶质细胞的形态，减少了小胶质细胞的簇形成，并减轻了SNc中的DA细胞死亡，并降低了中脑IL-1β的表达。这些结果表明，活化的小胶质细胞至少部分且特别是在初始阶段，有助于zi / zi大鼠SNc中的DA细胞死亡。