Amelioration of neurotoxic effects of HIV envelope protein gp120 by fibroblast growth factor: A strategy for neuroprotection

Approximately two thirds of patients with human immunodeficiency virus ence phalitis (HIVE) show cognitive impairment and neurodegeneration, while one third are cognitively unimpaired and their neuronal populations are preserv ed. Thus, it is possible that these individuals might have the capacity to produce neurotrophic factors capable of protecting neurons against the dele terious effects of HIV. In this context, the main objective of this study w as to determine whether fibroblast growth factor 1 (FGF1) is protective aga inst HIV. For this purpose levels of FGF1 immunoreactivity were determined in the frontal cortex of 35 AIDS cases subdivided into 4 groups according t o the presence or absence of HIVE and neurodegeneration. In cases without b oth HIVE and neurodegeneration, mild to moderate levels of FGF1 immunoreact ivity were observed in pyramidal neurons, while in cases with HIVE but with out neurodegeneration, levels were significantly elevated. In contrast, ind ividuals with both HIVE and neurodegeneration showed low levels of neuronal FGF1 immunoreactivity. Furthermore, studies in primary human neuronal cult ures treated with the HN envelope protein-gp120 in the presence or absence of FGF1 showed that FGF1 was protective against gp120 neurotoxicity in a do se-dependent manner. Taken together, these results support the notion that upregulation of certain neurotrophic factors, such as FGF1, might protect t he central nervous system from the neurotoxic effects of HIV.