Hill J M, Mervis R F, Avidor R, Moody T W, Brenneman D E
Unit on Neurochemistry, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Brain Res. 1993 Feb 19;603(2):222-33. doi: 10.1016/0006-8993(93)91241-j.
Cognitive and motor impairment are common symptoms among patients infected with the human immunodeficiency virus (HIV), including children who suffer neurological deficits and are frequently developmentally impaired. The HIV envelope protein, gp120, which has been shown to be toxic to neurons in culture, is shed in abundance by infected cells, and thus may play a significant role in the neuropathology of AIDS. To test this possible mechanism, neonatal rats were injected systemically with purified gp120 and the following consequences were observed: (1) radiolabeled gp120 and toxic fragments thereof were recovered in brain homogenates; (2) dystrophic changes were produced in pyramidal neurons of cerebral cortex; (3) retardation was evident in developmental milestones associated with complex motor behaviors. In parallel studies, co-treatment with peptide T, a gp120-derived peptide having a pentapeptide sequence homologous with vasoactive intestinal peptide, prevented or attenuated the morphological damage and behavioral delays associated with gp120 treatment. These studies suggest that gp120 and gp120-derived toxic fragments may contribute to the neurological and neuropsychiatric impairment related to HIV infection, and that peptide T appears to be effective in preventing gp120-associated neurotoxicity in developing rodents.
认知和运动障碍是感染人类免疫缺陷病毒（HIV）的患者常见症状，包括患有神经功能缺损且经常出现发育障碍的儿童。HIV包膜蛋白gp120在培养中已显示对神经元有毒性，被感染细胞大量释放，因此可能在艾滋病神经病理学中起重要作用。为了验证这一可能机制，对新生大鼠进行全身注射纯化的gp120，并观察到以下结果：（1）在脑匀浆中回收了放射性标记的gp120及其毒性片段；（2）大脑皮质锥体细胞出现营养不良性改变；（3）与复杂运动行为相关的发育里程碑出现明显迟缓。在平行研究中，用肽T（一种具有与血管活性肠肽同源的五肽序列的gp120衍生肽）进行联合治疗，可预防或减轻与gp120治疗相关的形态学损伤和行为延迟。这些研究表明，gp120和gp120衍生的毒性片段可能导致与HIV感染相关的神经和神经精神损害，并且肽T似乎能有效预防发育中的啮齿动物出现与gp120相关的神经毒性。
