Brain-derived neurotrophic factor prevents human immunodeficiency virus type 1 protein gp120 neurotoxicity in the rat nigrostriatal system
Brain-derived neurotrophic factor prevents human immunodeficiency virus type 1 protein gp120 neurotoxicity in the rat nigrostriatal system
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DOI：
10.1196/annals.1403.010
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发表时间：
2007-01-01
期刊：
影响因子：
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通讯作者：
Meyer, Edwin M.
中科院分区：
文献类型：
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作者：
Mocchetti, Italo;Nosheny, Rachel L.;Meyer, Edwin M.
人类免疫缺陷病毒1型（HIV-1）导致神经元变性，并在后期阶段，产生HIV相关痴呆（HAD）和其他神经系统异常。因此，对神经保护剂的需求是巨大的。然而，降低HIV神经毒性的治疗剂难以表征和开发，因为啮齿动物不受HIV感染。本研究利用HIV-1包膜糖蛋白120（gp 120）建立了HIV神经毒性动物模型。在成年大鼠的纹状体中急性注射媒介物或gp 120。如用于细胞凋亡的脑切片的组织化学分析和多巴胺的生物化学测定所示，GP 120产生黑质纹状体神经元的损失。神经营养因子脑源性神经营养因子（BDNF）的重组腺相关病毒载体提供防止gp 120的毒性。这项研究的结果支持这样的观点，即gp 120产生了广泛的神经毒性，类似于在HIV阳性个体中观察到的毒性，BDNF可能是HAD的合适的神经保护剂。
Human immunodeficiency virus type 1 (HIV-1) causes neuronal degeneration and, at a late stage, creates HIV-associated dementia (HAD) and other neurological abnormalities. Therefore, the need for neuroprotective agents is great. However, therapeutic agents that reduce HIV neurotoxicity are difficult to characterize and develop because rodents are not infected by HIV. This study was undertaken to develop an animal model of HIV neurotoxicity by using the HIV-1 envelope glycoprotein 120 (gp120). Vehicle or gp120 was injected acutely in the striatum of adult rats. gp120 produced loss of nigrostriatal neurons, as shown both by histochemical analysis of brain sections for apoptosis and biochemical determination of dopamine. The neurotrophin brain-derived neurotrophic factor (BDNF) delivered by a recombinant adeno-associated viral vector prevented gp120 toxicity. This study's results support the notion that gp120 produces a widespread neurotoxicity similar to that observed in HIV-positive individuals and that BDNF may be a suitable neuroprotective agent for HAD.