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M9550148.TXT
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1995-03-04
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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).