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 encephalitis (HIVE) show cognitive impairment and neurodegeneration, while one third are cognitively unimpaired and their neuronal populations are preserved. Thus, it is possible that these individuals might have the capacity to produce neurotrophic factors capable of protecting neurons against the deleterious effects of HIV. In this context, the main objective of this study was to determine whether fibroblast growth factor 1 (FGF1) is protective against HIV. For this purpose levels of FGF1 immunoreactivity were determined in the frontal cortex of 35 AIDS cases subdivided into 4 groups according to the presence or absence of HIVE and neurodegeneration. In cases without both HIVE and neurodegeneration, mild to moderate levels of FGFI immunoreactivity were observed in pyramidal neurons, while in cases with HIVE but without neurodegeneration, levels were significiantly elevated. In contrast, individuals with both HIVE and neurodegeneration showed low levels of neuronal FGF1 immunoreactivity. Furthermore, studies in primary human neuronal cultures treated with the HIV envelope protein-gp120 in the presence or absence of FGF1 showed that FGF1 was protective against gpl20 neurotoxicity in a dose-dependent manner. Taken together, these results support the notion that upregulation of certain neurotrophic factors, such as FGF1, might protect the central nervous system from the neurotoxic effects of HIV.
Institute of Psychiatry, DeCrespigny Park, London, United Kingdom.
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IP
Everall
G
G
Trillo-Pazos
C
C
Bell
M
M
Mallory
V
V
Sanders
E
E
Masliah
D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000378:metabolism*; D000328:Adult; D002478:Cells, Cultured; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism*; D009498:Neurotoxins / Q000378:metabolism / Q000633:toxicity*
D015699:HIV Envelope Protein gp120; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016220:Fibroblast Growth Factor 1