Central nervous system correlates of behavioral deficits following simian immunodeficiency virus infection.
Central nervous system correlates of behavioral deficits following simian immunodeficiency virus infection.
复制标题
中枢神经系统与猿猴免疫缺陷病毒感染后的行为缺陷相关。
DOI：
10.1080/13550280390218751
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发表时间：
2003
影响因子：
3.2
通讯作者：
Zink,MChristine
中科院分区：
文献类型：
--
作者：
Weed,MichaelR;Hienz,RobertD;Brady,JosephV;Adams,RobertJ;Mankowski,JosephL;Clements,JaniceE;Zink,MChristine
尽管获得性免疫缺陷综合征（AIDS）患者的认知和运动障碍的发生率很高，但AIDS相关中枢神经系统（CNS）病理学机制尚未完全了解。猴免疫缺陷病毒（SIV）感染猕猴提供了一个很好的艾滋病模型，包括人类免疫缺陷病毒（HIV）诱导的CNS病理和认知/行为障碍。共接种两种SIV毒株SIV/17 E-Fr和SIV/DeltaB 670可加速SIV CNS疾病，在3个月内在超过90%的猪尾猕猴中产生SIV脑炎。在本研究中，这种SIV模型被用来确定SIV感染后行为障碍的细胞和病毒相关性。SIV病对精神速度（简单反应时间）、精细运动控制（双手运动任务）和一般运动活动（笼内运动）都有不利影响。在安乐死之前，在12只猴子中的6只中的简单反应时间任务和6只猴子中的5只中的双手运动任务中，表现均显著受损。评价的所有猴（11/11）均显示自发运动活动显著减少。在双手运动测试的受损表现与轴突损伤（胼胝体中β-淀粉样前体蛋白的积累）以及增加的小胶质细胞活化和巨噬细胞浸润（CD 68和Ham 56免疫染色水平）之间发现了显著相关性。这些结果表明，轴突损伤与SIV感染引起的行为障碍有关。轴突损伤可能是由神经免疫反应引起的，包括小胶质细胞和巨噬细胞的激活。因此，轴突损伤可能是神经元功能障碍的形态学表现，是HIV/SIV CNS感染中行为障碍发展的基础。
Despite the high incidence of cognitive and motor impairment in acquired immunodeficiency syndrome (AIDS) patients, the mechanisms of AIDS-related central nervous system (CNS) pathology are not completely understood. Infection with simian immunodeficiency virus (SIV) in macaques provides an excellent model of AIDS, including human immunodeficiency virus (HIV)-induced CNS pathology and cognitive/behavioral impairment. Co-inoculation with two SIV strains, SIV/17E-Fr and SIV/DeltaB670, accelerates SIV CNS disease, producing SIV encephalitis in over 90% of pig-tailed macaques within 3 months. In the present study, this SIV model was employed to identify cellular and viral correlates of behavioral impairment following SIV infection. Measures of psychomotor speed (simple reaction time), fine motor control (bimanual motor task), and general motor activity (home cage movement) were all adversely affected by SIV disease. Prior to euthanasia, performance was significantly impaired in both a simple reaction time task in 6 of 12 monkeys and a bimanual motor task in 5 of 6 monkeys. All monkeys evaluated (11 of 11) showed significant reductions in spontaneous motor activity. Significant correlations were found between impaired performance on the bimanual motor test and axonal damage (accumulation of β-amyloid precursor protein in the corpus callosum) as well as increased microglial activation and macrophage infiltration (levels of CD68 and Ham56 immunostaining). These results suggest that axonal damage is related to the behavioral impairment induced by infection with SIV. The axonal damage may result from neuroimmune responses, including microglial and macrophage activation. Therefore, axonal damage may be a morphologic manifestation of neuronal dysfunction that underlies development of behavioral impairment in HIV/SIV CNS infection.