PREVENTION OF HIV-1 GP120-INDUCED NEURONAL DAMAGE IN THE CENTRAL-NERVOUS-SYSTEM OF TRANSGENIC MICE BY THE NMDA RECEPTOR ANTAGONIST MEMANTINE

To investigate the in vivo role of NMDA receptor stimulation in HIV-1- related CNS neurotoxicity, we evaluated the neuroprotective potential of the NMDA receptor antagonist memantine in transgenic mice which hav e gp120-induced CNS damage. Brains of mice treated chronically with me mantine and of untreated controls were analysed for structural damage by laser scanning confocal microscopy of sections immunolabeled for mi crotubule-associated protein-2 (MAP-2) and synaptophysin. Qualitative and quantitative analysis of confocal images revealed that memantine t reatment substantially decreased neuropathology in gp120 transgenic mi ce; this included statistically significant improvements in both dendr itic and presynaptic terminal density. These results provide in vivo e vidence that gp120 can activate neurotoxic pathways that can ultimatel y result in aberrant NMDA receptor stimulation and neuronal damage in the CNS. They also suggest that clinically tolerated NMDA receptor ant agonists may be useful in the prevention of neuronal damage in HIV-1-i nfected patients.