HIV-1 Inhibits Long-Term Potentiation and Attenuates Spatial Learning

Sheng Tian Li, Masayuki Matsushita, Akiyoshi Moriwaki, Yasunori Saheki, Yun Fei Lu, Kazuhito Tomizawa, Hai Yan Wu, Hiroaki Terada, Hideki Matsui

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43 Citations (Scopus)

Abstract

Although memory deficits have been dearly documented in patients with human immunodeficiency virus type-1 (HIV-1) infection, the physiological basis of this dysfunction is poorly understood. We focused on Tat, a viral protein released from HIV-1-infected cells and investigated its effect on spatial learning in adult mice. An intracerebroventricular injection of Tat leads to attenuation of spatial learning accompanied by suppression of long-term potentiation (LTP), the cellular basis of spatial learning, in hippocampal cornu ammonis 1 pyramidal neurons. Tat facilitates extrasynaptic but not synaptic N-methyl-D-aspartate (NMDA) receptor activity. Taken together, these data provide strong evidence that the Tat pathway underlies the development of memory dysfunction in patients with HIV-1 infection and suggest a causal relationship between Tat, the facilitation of extrasynaptic NMDA receptor activity, inhibition of LTP, and attenuation of spatial learning.

Original languageEnglish
Pages (from-to)362-371
Number of pages10
JournalAnnals of Neurology
Volume55
Issue number3
DOIs
Publication statusPublished - Mar 1 2004

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Li, S. T., Matsushita, M., Moriwaki, A., Saheki, Y., Lu, Y. F., Tomizawa, K., Wu, H. Y., Terada, H., & Matsui, H. (2004). HIV-1 Inhibits Long-Term Potentiation and Attenuates Spatial Learning. Annals of Neurology, 55(3), 362-371. https://doi.org/10.1002/ana.10844