PMID- 18077570 OWN - NLM STAT- MEDLINE DCOM- 20080421 LR - 20131121 IS - 0077-8923 (Print) IS - 0077-8923 (Linking) VI - 1122 DP - 2007 Dec TI - Brain-derived neurotrophic factor prevents human immunodeficiency virus type 1 protein gp120 neurotoxicity in the rat nigrostriatal system. PG - 144-54 AB - Human immunodeficiency virus type 1 (HIV-1) causes neuronal degeneration and, at a late stage, creates HIV-associated dementia (HAD) and other neurological abnormalities. Therefore, the need for neuroprotective agents is great. However, therapeutic agents that reduce HIV neurotoxicity are difficult to characterize and develop because rodents are not infected by HIV. This study was undertaken to develop an animal model of HIV neurotoxicity by using the HIV-1 envelope glycoprotein 120 (gp120). Vehicle or gp120 was injected acutely in the striatum of adult rats. gp120 produced loss of nigrostriatal neurons, as shown both by histochemical analysis of brain sections for apoptosis and biochemical determination of dopamine. The neurotrophin brain-derived neurotrophic factor (BDNF) delivered by a recombinant adeno-associated viral vector prevented gp120 toxicity. This study's results support the notion that gp120 produces a widespread neurotoxicity similar to that observed in HIV-positive individuals and that BDNF may be a suitable neuroprotective agent for HAD. FAU - Mocchetti, Italo AU - Mocchetti I AD - Department of Neuroscience, Georgetown University Medical Center, Research Bldg., 3970 Reservoir Rd., NW, Washington, DC 20057, USA. moccheti@georgetown.edu FAU - Nosheny, Rachel L AU - Nosheny RL FAU - Tanda, Gianluigi AU - Tanda G FAU - Ren, Ke AU - Ren K FAU - Meyer, Edwin M AU - Meyer EM LA - eng GR - NS040670/NS/NINDS NIH HHS/United States GR - NS046234/NS/NINDS NIH HHS/United States GR - NS047977/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Review PL - United States TA - Ann N Y Acad Sci JT - Annals of the New York Academy of Sciences JID - 7506858 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (HIV Envelope Protein gp120) RN - 0 (Neuroprotective Agents) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Brain-Derived Neurotrophic Factor/*therapeutic use MH - Corpus Striatum/*drug effects/metabolism/pathology MH - Disease Models, Animal MH - Dopamine/metabolism MH - HIV Envelope Protein gp120/*toxicity MH - Humans MH - Neurons/drug effects MH - Neuroprotective Agents/*therapeutic use MH - *Neurotoxicity Syndromes/etiology/pathology/prevention & control MH - Rats RF - 45 EDAT- 2007/12/14 09:00 MHDA- 2008/04/22 09:00 CRDT- 2007/12/14 09:00 PHST- 2007/12/14 09:00 [pubmed] PHST- 2008/04/22 09:00 [medline] PHST- 2007/12/14 09:00 [entrez] AID - 1122/1/144 [pii] AID - 10.1196/annals.1403.010 [doi] PST - ppublish SO - Ann N Y Acad Sci. 2007 Dec;1122:144-54. doi: 10.1196/annals.1403.010.