Differential long-term neurotoxicity of HIV-1 proteins in the rat hippocampal formation: A design-based stereological study

Differential long-term neurotoxicity of HIV-1 proteins in the rat hippocampal formation: A design-based stereological study
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DOI:
10.1002/hipo.20376
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发表时间:
2008-01-01
期刊:
影响因子:
3.5
通讯作者:
Mactutus, Charles F.
Mactutus, Charles F.
中科院分区:
医学3区
文献类型:
--
作者:
Fitting, Sylvia;Booze, Rosemarie M.;Mactutus, Charles F.

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人类免疫缺陷病毒 1 型 (HIV-1) 蛋白 gp120 和 Tat 被认为在介导 HIV-1 感染患者的中枢神经系统 (CNS) 病理学中发挥作用。使用基于设计的体视学,我们检查了新生儿海马内注射 gp120 和 Tat 对成人海马(类似于 71/2 个月)的作用。出生后第1天(P)1处理的Sprague-Dawley大鼠双侧注射媒介物(VEH,0.5μl无菌缓冲液)、gp120(100ng)、Tat(25μg)或组合的gp120+Tat(100ng+25μg)。使用尼西染色的组织切片,我们定量了大鼠海马五个亚区的总神经元[颗粒层(GL)、齿状回门(DGH)、角氨场(CA)2/3、CA1和下托(SUB)],以及两个亚区(DGH和SUB)的总神经胶质细胞(星形胶质细胞和少突胶质细胞)。在 DGH 中估算细胞面积和细胞体积。 Tat 和 gp120 使 CA2/3 子区的神经元数量显着减少,仅 Tat 使 DGH 显着减少。对于神经胶质细胞,Tat 蛋白增加了 DGH 和 SUB 中星形胶质细胞的数量,而 gp120 没有发现任何影响。最后,对于少突胶质细胞,Tat 增加了 DGH 中的细胞数量,但没有增加任何其他区域的细胞数量。 gp120 在任何大脑区域均未检测到影响。对三种不同细胞类型的细胞面积和细胞体积的估计显示处理之间没有显着差异。总的来说,这些结果表明 gp120 和 Tat 对估计的神经元总数以及神​​经胶质细胞的数量有不同的影响。 (c) 2007 年 Wiley-Liss, Inc.
The human immunodeficiency virus type 1 (HIV-1) proteins, gp120 and Tat, are believed to play a role in mediating central nervous system (CNS) pathology in HIV-1 infected patients. Using design-based stereology, we examined the role of neonatal intrahippocampal injections of gp120 and Tat on the adult hippocampus (similar to 71/2 month). Postnatal day (P)l-treated Sprague-Dawley rats were bilaterally injected with vehicle (VEH, 0.5 mu l sterile buffer), gp120 (100 ng), Tat (25 mu g) or combined gp120 + Tat (100 ng + 25 mu g). Using Nissi-stained tissue sections, we quantified total neurons in five subregions of the rat hippocampus [granual layer (GL), hilus of the dentate gyrus (DGH), cornu ammonis fields (CA)2/3, CA1, and subiculum (SUB)], and total glial cells (astrocytes and oligodendrocytes) in two subregions (DGH and SUB). Estimates of cell area and cell volume were taken in the DGH. There was a significant reduction of neuron number in the CA2/3 subfield by Tat and gp120, and a significant reduction in the DGH by Tat only. For glial cells, numbers of astrocytes in the DGH and SUB were increased by the Tat protein, whereas no effects were noted for gp120. Finally, for oligodendrocytes Tat increased cell number in the DGH but not in any other region; gp120 had no detectable effect in any brain region. Estimates of cell area and cell volume of the three different cell types revealed no significant differences between treatments. Collectively, these results suggest differential effects of gp120 and Tat on the estimated total number of neurons, as well as on the number of glial cells. (c) 2007 Wiley-Liss, Inc.