Study of receptor-mediated neurotoxins released by HIV-1-infected mononuclear phagocytes found in human brain

Dana Giulian, Jiahan Yu, Xia Li, Donald Tom, Jun Li, Elaine Wendt, Shen Nan Lin, Robert Schwarcz, Christine Noonan

Research output: Contribution to journalArticlepeer-review

139 Scopus citations

Abstract

Although there is growing evidence that neurotoxic molecules produced by HIV-1-infected mononuclear phagocytes damage neurons, the precise mechanisms of neuronal attack remain uncertain. One class of cytotoxin involves neuronal injury mediated via the NMDA receptor. We examined blood monocytes and brain mononuclear cells isolated at autopsy from HIV-1-infected individuals for the ability to release NMDA-like neuron-killing factors. We found that a neurotoxic amine, NTox, was produced by blood monocytes and by brain mononuclear phagocytes infected with retrovirus. In vivo injections of minute quantities of NTox produced selective damage to hippocampal pyramidal neurons. NTox can be extracted directly from brain tissues infected with HIV- 1 and showed structural features similar to wasp and spider venoms. In contrast to NTox, HIV-1 infection did not increase the release of the NMDA excitotoxin quinolinic acid (QUIN) from mononuclear cells. Although we found modest elevations of QUIN in the CSF of HIV-1-infected individuals, the increases were likely attributable to entry through damaged blood-brain barrier. Taken together, our data pinpoint NTox, rather than QUIN, as a major NMDA receptor-directed toxin associated with neuro-AIDS.

Original languageEnglish (US)
Pages (from-to)3139-3153
Number of pages15
JournalJournal of Neuroscience
Volume16
Issue number10
DOIs
StatePublished - May 15 1996

Keywords

  • AIDS
  • HIV- 1
  • NMDA
  • brain
  • dementia
  • gp120
  • macrophage
  • microglia
  • neurotoxin
  • quinolinic acid

ASJC Scopus subject areas

  • Medicine(all)

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