Pathogenesis of HIV encephalopathy : Specific binding of gp 120 to glycolipids in brain

HIV 脑病的发病机制：gp 120 与脑中糖脂的特异性结合

• 批准号: 04807034
• 负责人: KIMURA Junko
• 金额: $ 1.22万
• 依托单位: TOKYO METROPOLITAN INSTITUTE FOR NEUROSCIENCES
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04807034/
• 关键词: HIV encephalophathy; HIV-1 gp120; glycolipid; Brain culture; Demyelination; Neuronal death; HIV-1 gp120

In HIV encephalopathy, diffuse demyelination and neuronal loss have been observed frequently, while the pathogenesis of the damage remains obscure. Althourhg the neurotoxicity of gp120 as a causative factor ahs been reported, it is still not recognized. To clarify the neurotoxicity of gp120, its effects on neural cells were examined in rat primary culture of cerebral cortex.In immature neural cells, gp120 bound to most of neurons and the addition of gp120 (100nM) caused approximately 50% of neuronal death. The toxicity of gp120 against neurons was confirmed its own effect but not due to the contamination of endotoxin or mycoplasma.While in mature neural cells, gp120 bound to most of oligodendrocytes (Oligo), a small population of type-2 astrocytes and a few small neurons. The addition of gp120 (50-100nM) did not show any tozicity against neurons, but it resulted in significant inhibition of myelin formation. Gp120 can cause a functional disorder of Oligo, because the number of Oligo was not different but their processes were reduced in length and arborization compared with the control. Production of TNF alpha was not detected in gp120-treated culture.These results show that gp120 might have at least two separate effects on Oligo and neurons under certain conditions. The effects of HIV-1 gp120 could be an explanation for both neuronal loss and diffuse demyelination in HIV encephalopathy.

在HIV脑病中，经常观察到弥漫性脱髓鞘和神经元丧失，而损害的发病机理仍然晦涩难懂。据报道，gp120的神经毒性被报道了，但仍未识别出来。为了阐明GP120的神经毒性，在大鼠的大鼠原发性培养物中检查了其对神经细胞的作用。​​在未成熟的神经细胞中，GP120与大多数神经元结合，并添加GP120（100NM），导致大约50％的神经元死亡。 GP120对神经元的毒性得到了自身的作用，但并非由于内毒素或支原体的污染。当成熟的神经细胞中，GP120与大多数少突胶质细胞（OLIGO）结合，是少数少突胶质细胞（OLIGO），这是一个小的2型星形胶质细胞和几个小体系神经元。 GP120（50-100nm）的添加没有显示出对神经元的任何神经性，但导致对髓磷脂形成的显着抑制作用。 GP120会引起寡核的功能障碍，因为寡核的数量没有差异，但与对照相比，它们的过程的长度和树博化降低了。在GP120处理的培养物中未检测到TNFα的产生。这些结果表明，在某些条件下，GP120可能对寡核和神经元至少有两个单独的影响。 HIV-1 GP120的影响可能是HIV脑病中神经元丧失和弥漫性脱髓鞘的解释。

项目成果

Kimura-Kuroda,J.,Nagashima,K.,& Yasui,K.: "Inhibition of myelin formation by HIV-1 gp120 in rat cerebral cortex culture." Archives of Virology. in press.(1994)

木村黑田，J.，长岛，K.，

Kimura-Kuroda, J.Nagashima, K., & Yasuik, K.: "Inhibition of myelin formation by HIV-1 gp120 in rat cerebral cortex culture" Archives of Virology. (in press). (1994)

木村黑田，J.Nagashima，K.，

Kimura-Kuroda,J.,Nagashima,K.,&Yasui,K.: "HIV-1 gp120 causes demyelination in a primary culture of rat cerebral cortex." Clinical Neurolpathology. 12. 3 (1993)

木村黑田，J.，长岛，K.，

Kimura-Kuroda, J.Nagashima, K., & Yasuik, K.: "HIB-1 gp120 causes demyelination in a primary culture of rat cerebral cortex" Clinical Neuropathology. 12 : 3. (1993)

木村黑田，J.Nagashima，K.，

Kimura-Kuroda,J.,Nagashima,K.,&Yasui,K.: "Inhibition of myelin formation by HIV-1 gp120 in rat cerebral cortex culture." Archives of Virology. (in press.). (1994)

木村黑田，J.，长岛，K.，