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Role of the NMDA Receptor in Neuronal Apoptosis and HIV-Associated Dementia

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Glutamate and Addiction

Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

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Abstract

Neuronal injury and apoptosis may account, at least in part, for neurological complications associated with human immunodeficiency virus (HIV)-1 infection ranging from mild cognitive and motor impairment to dementia. The primary cell types infected in the brain are macrophages and microglia. These cells have been found in vivo and in vitro to release neurotoxic factors. Evidence has accumulated that neuronal apoptosis in HIV-related insults occurs predominantly via an indirect pathway comprising a complex cooperation of cytokines, reactive oxygen species and reactive nitrogen species, lipid mediators, and excitotoxins. These molecules lead to excessive stimulation of the N-methyl-Daspartate subtype of glutamate receptor (NMDAR). Of note, chemokine receptors, which, in conjunction with CD4, mediate HIV infection of macrophages/microglia, are present on neurons and astrocytes in addition to macrophages/microglia. Thus, these receptors potentially allow direct interaction between the virus and neurons (Fig. 2). The fact that specific chemokines ameliorate HIV/gp120induced neuronal apoptosis that is mediated by NMDARs suggests a functional connection between the receptors for chemokines and NMDA. Accordingly, here we review the role of the NMDAR in HIV-1-related and excitotoxic neuronal cell death.

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Authors
  1. Marcus Kaul PhD
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  2. Stuart A. Lipton MD,PhD
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Editor information

Editors and Affiliations

  1. Clinical Medical Branch, Division of Treatment Research and Development, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Bethesda, MD, USA

    Barbara H. Herman PhD

  2. Pharmacology, Integrative & Cellular Neurobiology Research Branch (PICNRB), Division of Neuroscience & Behavioral Research (DNBR), National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Bethesda, MD, USA

    Jerry Frankenheim PhD

  3. Treatment Research Branch, Division of Clinical and Prevention Research, National Institute on Drug Abuse (NIAAA), National Institutes of Health (NIH), Bethesda, MD, USA

    Raye Z. Litten PhD

  4. Division of Neuropharmacological Drug Products Center for Drug Evaluation and Research, Office of Drug Evaluation I, Food and Drug Administration, Rockville, MD, USA

    Philip H. Sheridan MD

  5. Laboratory of Molecular and Cellular Neurobiology, Division of Intramural Clinical and Biological Research, National Institute on Drug Abuse (NIAAA) National Institutes of Health (NIH), Bethesda, MD, USA

    Forrest F. Weight MD

  6. Division of Treatment Research and Development, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Bethesda, MD, USA

    Steven R. Zukin MD

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© 2002 Springer Science+Business Media New York

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Kaul, M., Lipton, S.A. (2002). Role of the NMDA Receptor in Neuronal Apoptosis and HIV-Associated Dementia. In: Herman, B.H., Frankenheim, J., Litten, R.Z., Sheridan, P.H., Weight, F.F., Zukin, S.R. (eds) Glutamate and Addiction. Contemporary Clinical Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-306-4_5

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  • DOI: https://doi.org/10.1007/978-1-59259-306-4_5

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-234-6

  • Online ISBN: 978-1-59259-306-4

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