Bansal A K, Mactutus C F, Nath A, Maragos W, Hauser K F, Booze R M
Department of Anatomy and Neurobiology, MN-224, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536, USA.
Brain Res. 2000 Oct 6;879(1-2):42-9. doi: 10.1016/s0006-8993(00)02725-6.
HIV-associated dementia complex is a serious disabling disease characterized by cognitive, behavioral and motor dysfunction. Basal ganglia involvement in HIV-1 infection may be responsible for some of the psychomotor symptoms associated with HIV dementia. The objectives of the present study were to determine: (1) whether gp120 and Tat produce striatal toxicity, and (2) whether gp120 and Tat show synergistic toxicity in the striatum. In these studies, the recombinant proteins gp120, Tat, or saline (0.9%) were stereotaxically injected in the striatum of adult male rats. The striatal sections were evaluated for area of tissue loss (Cresyl-violet stained sections) and the number of GFAP immunoreactive cells 7 days after the injections. Doses of gp120 250 ng/microl or higher and Tat 5 microg/microl or higher produced a significant area of tissue loss and significantly increased the number of GFAP reactive cells. We found no toxicity in animals treated with immunoabsorbed gp120 or Tat. Combined gp120 (100 ng/microl)+Tat (1 microg/microl) injections into the rat striatum significantly increased the area of tissue loss and altered morphology and increased number of GFAP reactive cells, as compared to controls. Thus, the present results suggest the involvement of gp120 and Tat in striatal toxicity and provide a model for further studies to fully characterize their role in HIV-1 toxicity and to develop therapeutic strategies for HIV-1 associated dementia complex.
与人类免疫缺陷病毒（HIV）相关的痴呆综合征是一种严重的致残性疾病，其特征为认知、行为和运动功能障碍。基底神经节受累于HIV-1感染可能是与HIV痴呆相关的一些精神运动症状的原因。本研究的目的是确定：（1）糖蛋白120（gp120）和反式激活转录蛋白（Tat）是否产生纹状体毒性，以及（2）gp120和Tat在纹状体中是否表现出协同毒性。在这些研究中，将重组蛋白gp120、Tat或生理盐水（0.9%）立体定向注射到成年雄性大鼠的纹状体中。注射7天后，对纹状体切片进行组织损失面积（甲酚紫染色切片）和胶质纤维酸性蛋白（GFAP）免疫反应性细胞数量的评估。剂量为250纳克/微升或更高的gp120以及5微克/微升或更高的Tat产生了显著的组织损失面积，并显著增加了GFAP反应性细胞的数量。我们发现用免疫吸附的gp120或Tat处理的动物没有毒性。与对照组相比，将gp120（100纳克/微升）+Tat（1微克/微升）联合注射到大鼠纹状体中显著增加了组织损失面积，改变了形态，并增加了GFAP反应性细胞的数量。因此，目前的结果表明gp120和Tat参与了纹状体毒性，并为进一步研究提供了一个模型，以充分表征它们在HIV-1毒性中的作用，并开发针对与HIV-1相关的痴呆综合征的治疗策略。
