PMID- 7835247
OWN - NLM
STAT- MEDLINE
DCOM- 19950227
LR  - 20180214
IS  - 0378-5866 (Print)
IS  - 0378-5866 (Linking)
VI  - 15
IP  - 6
DP  - 1993
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.
PG  - 417-22
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.
FAU - Gelbard, H A
AU  - Gelbard HA
AD  - Department of Neurology, University of Rochester Medical Center, N.Y. 14642.
FAU - Dzenko, K A
AU  - Dzenko KA
FAU - DiLoreto, D
AU  - DiLoreto D
FAU - del Cerro, C
AU  - del Cerro C
FAU - del Cerro, M
AU  - del Cerro M
FAU - Epstein, L G
AU  - Epstein LG
LA  - eng
GR  - P01 NS31492-01/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Switzerland
TA  - Dev Neurosci
JT  - Developmental neuroscience
JID - 7809375
RN  - 0 (Receptors, AMPA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione)
SB  - IM
MH  - 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology
MH  - AIDS Dementia Complex/*pathology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Dizocilpine Maleate/pharmacology
MH  - Humans
MH  - Microscopy, Electron
MH  - Neurons/*drug effects/ultrastructure
MH  - Receptors, AMPA/*agonists/antagonists & inhibitors
MH  - Tumor Necrosis Factor-alpha/*toxicity
EDAT- 1993/01/01 00:00
MHDA- 1993/01/01 00:01
CRDT- 1993/01/01 00:00
PHST- 1993/01/01 00:00 [pubmed]
PHST- 1993/01/01 00:01 [medline]
PHST- 1993/01/01 00:00 [entrez]
AID - 10.1159/000111367 [doi]
PST - ppublish
SO  - Dev Neurosci. 1993;15(6):417-22. doi: 10.1159/000111367.