The final pathways for neuronal injury in human immunodeficiency virus type one (HIV-1)-associated dementia (HAD) were investigated in Xenopus oocytes expressing recombinant NR1a/NR2B N-methyl-D-aspartate (NMDA) receptors exposed to secretory products from HIV-infected macrophages. Pressure ejection of HIV-1-infected and CD40 ligand-stimulated human monocyte-derived macrophage (MDM) fluids produced inward currents in oocytes expressing NR1a/NR2B (30.2±5.1 nA, n=42, mean±SE), but not in uninjected cells. In contrast, control (uninfected MDM) fluids induced currents of 4.5±0.5 nA (n=17). Infected or stimulated MDM without virus showed intermediate responses. The induced currents were MDM fluid dose-dependant and blocked by the NMDA receptor antagonist 2-amino-5-phosphnovalerate (50 μM), but not by 6-cyano-7-nitroquinoxaline-2,3-dione (20 μM). Although low levels of glutamate were detected in the culture fluids, the addition of L-glutamate decarboxylase to the MDM did not significantly change the level of induced inward currents. Our experiments demonstrate that secretory factors from HIV-1-infected MDM activate NMDA receptors NR1a/NR2B and may contribute to neuronal demise during HAD.
- Human immunodeficiency virus
- N-methyl-D-aspartate receptor
- Voltage clamp
- Xenopus oocytes
ASJC Scopus subject areas