Premium
Human immunodeficiency virus type 1 tat activates non— N ‐methyl‐ D ‐aspartate excitatory amino acid receptors and causes neurotoxicity
Author(s) -
Magnuson David S. K.,
Knudsen Bodo E.,
Geiger Jonathan D.,
Brownstone Robert M.,
Nath Avindra
Publication year - 1995
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410370314
Subject(s) - neurotoxicity , antagonist , excitatory postsynaptic potential , tetrodotoxin , receptor , pharmacology , cytotoxicity , biology , chemistry , biochemistry , toxicity , endocrinology , in vitro , organic chemistry
The human immunodeficiency virus type 1 (HIV‐1) protein Tat is known to be released from HIV‐1‐infected cells. We show that micromolar concentrations of Tat depolarized young rat and adult human neurons. In addition, Tat, at similar concentrations, was toxic to human fetal neurons in culture. Tat‐induced responses were insensitive to the Na + channel blocker tetrodotoxin, suggesting a direct effect of Tat on neurons. Tat‐induced depolarizations and cytotoxicity were blocked by the excitatory amino acid antagonist kynurenate. The N ‐methylv D ‐aspartate receptor antagonist D v2vaminov5‐phosphonovalerate had little effect on Tatvinduced depolarizations but did provide protection from Tat neurotoxicity. These results suggest that Tat, released from HIVv1vinfected cells, may be an important mediator of neurotoxicity observed in HIV1 encephalopathy.