Impaired astrocytes and diffuse activation of microglia in the cerebral cortex in simian immunodeficiency virus-infected macaques without simian immunodeficiency virus encephalitis

Impaired astrocytes and diffuse activation of microglia in the cerebral cortex in simian immunodeficiency virus-infected macaques without simian immunodeficiency virus encephalitis
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DOI:
10.1097/nen.0b013e3181772ce0
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发表时间:
2008-06-01
影响因子:
3.2
通讯作者:
Izumo, Shuji
Izumo, Shuji
中科院分区:
医学4区
文献类型:
--
作者:
Xing, Hui Qin;Mori, Kazuyasu;Izumo, Shuji

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在获得性免疫缺陷综合征(AIDS)痴呆中已有各种类型的神经元损伤的报道。我们先前证明,在感染SIV的艾滋病痴呆猕猴模型中,炎症和皮质损伤根据病毒的嗜性而独立发生。为了阐明皮质变性的发病机制,我们对感染SIV的猕猴的额叶皮质进行了检查,发现星形胶质细胞中存在细胞凋亡和兴奋性氨基酸转运蛋白2的表达减少,弥漫性激活。小胶质细胞与有限的神经元损伤相关。一些激活的小胶质细胞也表达兴奋性氨基酸转运蛋白2,但不表达促炎细胞因子。大脑皮层或白质未见炎性改变,无论是免疫组织化学检测还是从显微解剖组织样本中提取的SIV基因组的聚合酶链式反应检测均未检测到SIV感染细胞。这些结果表明,星形胶质细胞的异常和小胶质细胞的代偿性激活可能对无SIV脑炎的SIV感染猕猴的额叶皮质神经元变性起到保护作用。
Various types of neuronal damage have been reported in acquired immunodeficiency syndrome (AIDS) dementia. We previously demonstrated that inflammation and cortical damage occur independently according to viral tropism in a simian immunodeficiency virus (SIV)-infected macaque model of AIDS dementia. To elucidate the pathogenesis of cortical degeneration, we examined the frontal cortex of SIV-infected macaques and found apoptosis and decreased expression of the excitatory amino acid transporter 2 in astrocytes and diffuse activation of. microglia in association with limited neuronal damage. Some activated microglia also expressed excitatory amino acid transporter 2 but not proinflammatory cytokines. No inflammatory changes were seen in the cortex or the white matter, and SIV-infected cells were not detected in or around cortical lesions either by immunohistochemistry or by the polymerase chain reaction detection of SIV genomes of extracted DNA from microdissected tissue samples. These results indicate that an astrocytic abnormality and a compensatory activation of microglia might provide a protective effect against neuronal degeneration in the frontal cortex of SIV-infected macaques without SIV encephalitis.