Document 0148
 DOCN  M9550148
 TI    Neurotoxic effects of tumor necrosis factor alpha in primary human
       neuronal cultures are mediated by activation of the glutamate AMPA
       receptor subtype: implications for AIDS neuropathogenesis.
 DT    9505
 AU    Gelbard HA; Dzenko KA; DiLoreto D; del Cerro C; del Cerro M; Epstein LG;
       Department of Neurology, University of Rochester Medical Center,; N.Y.
       14642.
 SO    Dev Neurosci. 1993;15(6):417-22. Unique Identifier : AIDSLINE
       MED/95136893
 AB    Human immunodeficiency virus type 1 (HIV) infection of the central
       nervous system is characterized by neuronal loss in discrete areas of
       the central nervous system. We have previously demonstrated that
       HIV-infected monocytes in culture with astroglial cells produce high
       levels (> or = 200 pg/ml) of the cytokine tumor necrosis factor-alpha
       (TNF alpha). We now demonstrate that TNF alpha (> or = 200 pg/ml) is
       neurotoxic to cultured primary human fetal cortical neurons at both
       light and electron microscopic levels. Subtoxic doses of TNF alpha (50
       pg/ml) are neurotoxic in combination with the glutamate
       (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA)
       subtype receptor agonist AMPA (100 microM). The neurotoxic effects of
       TNF alpha (200 pg/ml) are blocked in part by the AMPA receptor
       antagonist, 6-cyano-7-nitroquinoxaline-2, 3-dione (10 microM). This
       suggests that TNF alpha may exert neurotoxic effects on human neurons by
       indirect activation of AMPA receptors, which may be important in the
       pathogenesis and treatment of HIV-mediated encephalopathy.
 DE    AIDS Dementia Complex/*PATHOLOGY  Cell Survival/DRUG EFFECTS  Cells,
       Cultured  Dizocilpine Maleate/PHARMACOLOGY  Human  Microscopy, Electron
       Neurons/*DRUG EFFECTS/ULTRASTRUCTURE  Receptors,
       AMPA/*AGONISTS/ANTAGONISTS & INHIB  Support, Non-U.S. Gov't  Support,
       U.S. Gov't, P.H.S.  Tumor Necrosis Factor/*TOXICITY
       6-Cyano-7-nitroquinoxaline-2,3-dione/PHARMACOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).