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Synergistic neurotoxicity by human immunodeficiency virus proteins Tat and gp120: protection by memantine.
Ann Neurol. 2000 Feb; 47(2):186-94.AN

Abstract

Human immunodeficiency virus type 1 (HIV-1) proteins Tat and gp120 have been implicated in the pathogenesis of dementia associated with HIV infection. Recently, we showed the presence of Tat protein in brains of patients with HIV-1 encephalitis as well as macaques with encephalitis caused by a chimeric strain of HIV and simian immunodeficiency virus, and that even transient exposure of cells to Tat leads to release of cytopathic cytokines. Now, we report the first demonstration of gp120 protein in brain of patients with HIV encephalitis. We tested the hypothesis that Tat and gp120 would act synergistically to potentiate each protein's neurotoxic effects and determined the extent to which pharmacological antagonists against processes implicated in HIV-1 neuropathogenesis could block HIV-1 protein-induced neurotoxicity. Subtoxic concentrations of Tat and gp120, when incubated together, caused neuronal cell death and prolonged increases in levels of intracellular calcium. A transient exposure of neurons to Tat and gp120 for seconds initiated neuronal cell death, but maximal levels of neuronal cell death were observed with exposures lasting 30 minutes. The neurotoxicity caused by Tat and gp120 applied in combination was blocked completely by memantine, partially by amiloride, and not at all by dipyridamole or vigabatrin.

Authors+Show Affiliations

Department of Neurology, University of Kentucky, Lexington 40536-0284, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10665489

Citation

Nath, A, et al. "Synergistic Neurotoxicity By Human Immunodeficiency Virus Proteins Tat and Gp120: Protection By Memantine." Annals of Neurology, vol. 47, no. 2, 2000, pp. 186-94.
Nath A, Haughey NJ, Jones M, et al. Synergistic neurotoxicity by human immunodeficiency virus proteins Tat and gp120: protection by memantine. Ann Neurol. 2000;47(2):186-94.
Nath, A., Haughey, N. J., Jones, M., Anderson, C., Bell, J. E., & Geiger, J. D. (2000). Synergistic neurotoxicity by human immunodeficiency virus proteins Tat and gp120: protection by memantine. Annals of Neurology, 47(2), 186-94.
Nath A, et al. Synergistic Neurotoxicity By Human Immunodeficiency Virus Proteins Tat and Gp120: Protection By Memantine. Ann Neurol. 2000;47(2):186-94. PubMed PMID: 10665489.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synergistic neurotoxicity by human immunodeficiency virus proteins Tat and gp120: protection by memantine. AU - Nath,A, AU - Haughey,N J, AU - Jones,M, AU - Anderson,C, AU - Bell,J E, AU - Geiger,J D, PY - 2000/2/9/pubmed PY - 2000/2/19/medline PY - 2000/2/9/entrez SP - 186 EP - 94 JF - Annals of neurology JO - Ann Neurol VL - 47 IS - 2 N2 - Human immunodeficiency virus type 1 (HIV-1) proteins Tat and gp120 have been implicated in the pathogenesis of dementia associated with HIV infection. Recently, we showed the presence of Tat protein in brains of patients with HIV-1 encephalitis as well as macaques with encephalitis caused by a chimeric strain of HIV and simian immunodeficiency virus, and that even transient exposure of cells to Tat leads to release of cytopathic cytokines. Now, we report the first demonstration of gp120 protein in brain of patients with HIV encephalitis. We tested the hypothesis that Tat and gp120 would act synergistically to potentiate each protein's neurotoxic effects and determined the extent to which pharmacological antagonists against processes implicated in HIV-1 neuropathogenesis could block HIV-1 protein-induced neurotoxicity. Subtoxic concentrations of Tat and gp120, when incubated together, caused neuronal cell death and prolonged increases in levels of intracellular calcium. A transient exposure of neurons to Tat and gp120 for seconds initiated neuronal cell death, but maximal levels of neuronal cell death were observed with exposures lasting 30 minutes. The neurotoxicity caused by Tat and gp120 applied in combination was blocked completely by memantine, partially by amiloride, and not at all by dipyridamole or vigabatrin. SN - 0364-5134 UR - https://www.unboundmedicine.com/medline/citation/10665489/Synergistic_neurotoxicity_by_human_immunodeficiency_virus_proteins_Tat_and_gp120:_protection_by_memantine_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0364-5134&date=2000&volume=47&issue=2&spage=186 DB - PRIME DP - Unbound Medicine ER -