Bagetta G, Corasaniti M T, Aloe L, Berliocchi L, Costa N, Finazzi-Agrò A, Nisticò G
Department of Biology, Mondino-Tor Vergata Center for Experimental Neurobiology, Rome, Italy.
Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):928-33. doi: 10.1073/pnas.93.2.928.
We have studied the neuropathological characteristics of the brain of rats receiving daily intracerebroventricular administration of freshly dissolved human immunodeficiency virus type 1 recombinant protein gp120 (100 ng per rat per day) given for up to 14 days. Histological examination of serial brain sections revealed no apparent gross damage to the cortex or hippocampus, nor did cell counting yield significant neuronal cell loss. However, the viral protein caused after 7 and 14 days of treatment DNA fragmentation in 10% of brain cortical neurons. Interestingly, reduced neuronal nitric oxide synthase (NOS) expression along with significant increases in nerve growth factor (NGF) were observed in the hippocampus, where gp120 did not cause neuronal damage. No changes in NGF and NOS expression were seen in the cortex, where cell death is likely to be of the apoptotic type. The present data demonstrate that gp120-induced cortical cell death is associated with the lack of increase of NGF in the cerebral cortex and suggest that the latter may be important for the expression of neuropathology in the rat brain. By contrast, enhanced levels of NGF may prevent or delay neuronal death in the hippocampus, where reduced NOS expression may be a reflection of a subcellular insult inflicted by the viral protein.
我们研究了每日经脑室内给予新鲜溶解的人类免疫缺陷病毒1型重组蛋白gp120（每只大鼠每天100纳克），持续给药长达14天的大鼠大脑的神经病理学特征。对连续脑切片进行组织学检查发现，皮层或海马体没有明显的大体损伤，细胞计数也未显示出明显的神经元细胞损失。然而，在治疗7天和14天后，病毒蛋白导致10%的脑皮层神经元出现DNA片段化。有趣的是，在gp120未引起神经元损伤的海马体中，观察到神经元型一氧化氮合酶（NOS）表达降低，同时神经生长因子（NGF）显著增加。在可能发生凋亡型细胞死亡的皮层中，未观察到NGF和NOS表达的变化。目前的数据表明，gp120诱导的皮层细胞死亡与大脑皮层中NGF缺乏增加有关，并表明后者可能对大鼠大脑神经病理学的表达很重要。相比之下，NGF水平升高可能会预防或延迟海马体中的神经元死亡，其中NOS表达降低可能反映了病毒蛋白造成的亚细胞损伤。
