Berman N E, Yong C, Raghavan R, Raymond L A, Joag S V, Narayan O, Cheney P D
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City 66160-7400, USA.
Mol Chem Neuropathol. 1998 May;34(1):25-38. doi: 10.1007/BF02815134.
Astrocyte activation has been postulated to be a major contributor to functional changes in the brain of AIDS patients. We assessed astrocyte activation in the simian immunodeficiency virus (SIV) model. Four groups of macaque brains were examined: uninoculated controls, animals inoculated with virus that did not cause disease, animals inoculated with virus that caused AIDS but did not cause encephalitis, and animals with SIV encephalitis. We examined expression of calbindin-D-28K, a calcium binding protein that is upregulated in astrocytes during excitotoxic events, as well as glial fibrillary acidic protein (GFAP). The presence of calbindin in astrocytes was confirmed by double-labeling using confocal microscopy. Increases in calbindin staining were most apparent in the white matter, but increases in GFAP staining were most apparent in middle layers of the cerebral cortex. Six of the seven animals with SIV encephalitis had calbindin immunoreactive astrocytes in the subcortical white matter, corpus callosum, internal capsule, cerebral peduncle, pontine white matter, and cerebellar white matter. Very rarely, a few, very lightly calbindin-immunoreactive astrocytes were present in the uninoculated control brains. The increase in calbindin expression by astrocytes in SIV encephalitis suggests that these cells are subject to calcium toxicity. In uninoculated control macaques, and in macaques inoculated with virus that did not cause disease, GFAP-immunoreactive astrocytes were present throughout the subcortical white matter and in layer I, but very few were found in layers III-V of the cerebral cortex. Two animals that died of AIDS without encephalitis had somewhat higher numbers of GFAP immunoreactive astrocytes in middle cortical layers. In seven animals that received passaged neurovirulent virus and developed both AIDS and encephalitis, the number of GFAP-immunoreactive astrocytes in middle cortical layers was high, indicating widespread astrocyte activation.
星形胶质细胞激活被认为是艾滋病患者大脑功能变化的主要促成因素。我们在猴免疫缺陷病毒（SIV）模型中评估了星形胶质细胞激活情况。检查了四组猕猴大脑：未接种的对照组、接种不会致病病毒的动物、接种会导致艾滋病但不会引起脑炎的病毒的动物以及患有SIV脑炎的动物。我们检测了钙结合蛋白-D-28K（一种在兴奋性毒性事件期间星形胶质细胞中上调的钙结合蛋白）以及胶质纤维酸性蛋白（GFAP）的表达。通过共聚焦显微镜双重标记证实了星形胶质细胞中钙结合蛋白的存在。钙结合蛋白染色增加在白质中最为明显，但GFAP染色增加在大脑皮质中层最为明显。七只患有SIV脑炎的动物中有六只在皮质下白质、胼胝体、内囊、脑桥、脑桥白质和小脑白质中有钙结合蛋白免疫反应性星形胶质细胞。在未接种的对照大脑中非常罕见地存在少数非常轻度钙结合蛋白免疫反应性星形胶质细胞。SIV脑炎中星形胶质细胞钙结合蛋白表达的增加表明这些细胞受到钙毒性影响。在未接种的对照猕猴以及接种不会致病病毒的猕猴中，GFAP免疫反应性星形胶质细胞存在于整个皮质下白质和I层，但在大脑皮质的III-V层中很少发现。两只死于艾滋病但无脑炎的动物在皮质中层有数量略多的GFAP免疫反应性星形胶质细胞。在七只接受传代神经毒性病毒并同时发展为艾滋病和脑炎的动物中，皮质中层GFAP免疫反应性星形胶质细胞数量很多，表明存在广泛的星形胶质细胞激活。
