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- Title
Human immunodeficiency virus type 1 glycoprotein gp120 reduces the levels of brain-derived neurotrophic factorin vivo: potential implication for neuronal cell death.
- Authors
Nosheny, Rachel L.; Bachis, Alessia; Acquas, Elio; Mocchetti, Italo
- Abstract
Neuronal loss has been observed inpost mortembrains of patients with human immunodeficiency virus type 1 (HIV-1). Experimental evidence has implicated HIV-1-derived envelope glycoprotein 120 (gp120) in the neuronal cell death observed in these patients. However, the intrinsic mechanisms by which gp120 causes neurotoxicity are still unknown. We have recently shown that the neurotoxic effect of gp120in vitrois reduced by brain-derived neurotrophic factor (BDNF). We therefore tested the hypothesis that low levels of BDNF render neurons more sensitive to gp120. Gp120 was injected acutely into the striatum of BDNF heterozygous mice and wild-type littermates. BDNF heterozygous mice exhibited more apoptotic neurons in the striatum than wild-type mice, suggesting that BDNF is neuroprotective alsoin vivo.Because several neurodegenerative disorders are characterized by lack of trophic support, we tested the hypothesis that gp120 may cause apoptosis by reducing BDNF expression. Gp120 was injected acutely in the rat striatum and BDNF levels determined by a two-site immunoassay at various times after the injection. Gp120 elicited a dramatic decrease in BDNF protein levels by 24 h. Reduced BDNF levels were still present at 4 days. Cellular localization of BDNF immunoreactivity revealed that gp120 decreases BDNF immunoreactivity mainly in neuronal processes. This effect of gp120 precedes the peak of caspase-3 activation and neuronal cell death. We propose that one of the mechanisms whereby gp120 causes neurotoxicity is a reduction of the neurotrophic factor environment crucial for cell survival.
- Subjects
APOPTOSIS; HIV; GLYCOPROTEINS; NEUROTROPHINS; NEURONS; NEUROTOXICOLOGY; IMMUNOASSAY
- Publication
European Journal of Neuroscience, 2004, Vol 20, Issue 11, p2857
- ISSN
0953-816X
- Publication type
Article
- DOI
10.1111/j.1460-9568.2004.03764.x