首页 | 本学科首页   官方微博 | 高级检索  
     


Prevention of HIV-1 gp120-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine
Authors:Stephanie M. Toggas  Eliezer Masliah  Lennart Mucke
Affiliation:aDepartment of Neuropharmacology, Division of Virology, The Scripps Research Institute, 10666 North Torrey Pines Road, Mail Drop IMM-6, La Jolla, CA 92037, USA;bDepartments of Neurosciences and Pathology, University of California at San Diego, School of Medicine, La Jolla, CA 92093, USA
Abstract: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 have gp120-induced CNS damage. Brains of mice treated chronically with memantine and of untreated controls were analysed for structural damage by laser scanning confocal microscopy of sections immunolabeled for microtubule-associated protein-2 (MAP-2) and synaptophysin. Qualitative and quantitative analysis of confocal images revealed that memantine treatment substantially decreased neuropathology in gp120 transgenic mice; this included statistically significant improvements in both dendritic and presynaptic terminal density. These results provide in vivo evidence that gp120 can activate neurotoxic pathways that can ultimately result in aberrant NMDA receptor stimulation and neuronal damage in the CNS. They also suggest that clinically tolerated NMDA receptor antagonists may be useful in the prevention of neuronal damage in HIV-1-infected patients.
Keywords:Neurotoxicity   HIV-1   Transgenic   N-Methyl-d-aspartate   Glutamate   Treatment
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号