Human immunodeficiency virus type 1 tat activates non—N‐methyl‐D‐aspartate excitatory amino acid receptors and causes neurotoxicity

David S.K. Magnuson, Bodo E. Knudsen, Jonathan D. Geiger, Robert M. Brownstone, Avindra Nath

Research output: Contribution to journalArticle

249 Citations (Scopus)

Abstract

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‐methylvD‐aspartate receptor antagonist Dv2vaminov5‐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.

Original languageEnglish (US)
Pages (from-to)373-380
Number of pages8
JournalAnnals of Neurology
Volume37
Issue number3
DOIs
StatePublished - Mar 1995

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Glutamate Receptors
HIV-1
Neurons
Kynurenic Acid
Human Immunodeficiency Virus Proteins
Excitatory Amino Acid Antagonists
Poisons
Tetrodotoxin
Brain Diseases
Young Adult

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Human immunodeficiency virus type 1 tat activates non—N‐methyl‐D‐aspartate excitatory amino acid receptors and causes neurotoxicity. / Magnuson, David S.K.; Knudsen, Bodo E.; Geiger, Jonathan D.; Brownstone, Robert M.; Nath, Avindra.

In: Annals of Neurology, Vol. 37, No. 3, 03.1995, p. 373-380.

Research output: Contribution to journalArticle

Magnuson, David S.K. ; Knudsen, Bodo E. ; Geiger, Jonathan D. ; Brownstone, Robert M. ; Nath, Avindra. / Human immunodeficiency virus type 1 tat activates non—N‐methyl‐D‐aspartate excitatory amino acid receptors and causes neurotoxicity. In: Annals of Neurology. 1995 ; Vol. 37, No. 3. pp. 373-380.
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