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

在HIV脑病中，经常观察到弥漫性脱髓鞘和神经元丢失，而损伤的发病机制仍不清楚。尽管gp 120作为致病因子的神经毒性已有报道，但尚未得到认可。为了阐明gp 120的神经毒性，在大鼠大脑皮层原代培养中检测了其对神经细胞的影响，在未成熟的神经细胞中，gp 120与大多数神经元结合，并且gp 120（100 nM）的加入引起约50%的神经元死亡。gp 120对神经元的毒性已被证实是其自身作用，而不是由于内毒素或支原体的污染。而在成熟的神经细胞中，gp 120与大多数少突胶质细胞（Oligo）、一小群2型星形胶质细胞和少数小神经元结合。加入gp 120（50- 100 nM）对神经元没有任何毒性，但它导致髓鞘形成的显著抑制。Gp 120可引起Oligo功能紊乱，因为与对照相比，Oligo的数量没有变化，但它们的突起长度和树枝状化减少。这些结果表明，在一定条件下，gp 120可能对寡核苷酸和神经元至少有两种不同的作用。HIV-1 gp 120的作用可能是HIV脑病中神经元丢失和弥漫性脱髓鞘的一种解释。

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.