Prospéro-García O, Gold L H, Fox H S, Polis I, Koob G F, Bloom F E, Henriksen S J
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14158-63. doi: 10.1073/pnas.93.24.14158.
Four rhesus macaques were inoculated intravenously with a cryopreserved stock of microglia obtained from a simian immunodeficiency virus (SIV)-infected rhesus macaque. Before infection, three of the four monkeys were trained and tested daily on a computerized neuropsychological test battery. After SIV infection, behavioral testing continued to monitor deficits associated with disease progression. Five additional age-matched, behaviorally trained monkeys served as controls. Neurophysiological testing for visual and auditory evoked responses was accomplished 37-52 weeks after infection in all monkeys. Subsequently, all four SIV-infected monkeys and one control subject were sacrificed, and samples of brain tissue were taken for pathological analysis. SIV-infected monkeys demonstrated abnormal responses in both auditory and visual evoked responses. In addition, around the time of electrophysiological recording, all three SIV-infected, behaviorally trained monkeys exhibited significant decreases in progressive-ratio performance, reflecting a reduction in reinforcer efficacy. One subject also demonstrated impairments in shifting of attentional set and motor ability at that time. Neuropathological evaluation revealed that all four SIV-infected monkeys exhibited numerous perivascular and parenchymal infiltrating T cells. These findings document that SIV causes electrophysiological, behavioral, and neuropathological sequelae similar to what has been observed in the human neuroAIDS syndrome. Our observations further validate the simian model for the investigation of the pathogenesis of AIDS dementia and for the investigation of drugs with potential therapeutic benefits.
将来自一只感染了猿猴免疫缺陷病毒（SIV）的恒河猴的冷冻保存的小胶质细胞库存静脉注射到4只恒河猴体内。在感染前，4只猴子中的3只每天接受计算机化神经心理测试组的训练和测试。在感染SIV后，继续进行行为测试以监测与疾病进展相关的缺陷。另外5只年龄匹配、经过行为训练的猴子作为对照。在所有猴子感染后37 - 52周完成视觉和听觉诱发电位的神经生理学测试。随后，对所有4只感染SIV的猴子和1只对照猴子实施安乐死，并采集脑组织样本进行病理分析。感染SIV的猴子在听觉和视觉诱发电位中均表现出异常反应。此外，在进行电生理记录时，所有3只感染SIV且经过行为训练的猴子在渐进比率表现上均显著下降，这反映了强化物效力的降低。此时，1只猴子在注意力集转移和运动能力方面也表现出损伤。神经病理学评估显示，所有4只感染SIV的猴子均表现出大量血管周围和实质浸润的T细胞。这些发现证明，SIV会导致与人类神经艾滋病综合征中所观察到的类似的电生理、行为和神经病理学后遗症。我们的观察结果进一步验证了恒河猴模型在研究艾滋病痴呆症发病机制以及研究具有潜在治疗益处的药物方面的有效性。
