Brain-derived neurotrophic factor prevents human immunodeficiency virus type 1 protein gp120 neurotoxicity in the rat nigrostriatal system.
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.
Mocchetti
Italo
I
Department of Neuroscience, Georgetown University Medical Center, Research Bldg., 3970 Reservoir Rd., NW, Washington, DC 20057, USA. moccheti@georgetown.edu
Nosheny
Rachel L
RL
Tanda
Gianluigi
G
Ren
Ke
K
Meyer
Edwin M
EM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000627:therapeutic use*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000633:toxicity*; D006801:Humans; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D051381:Rats
D019208:Brain-Derived Neurotrophic Factor; D015699:HIV Envelope Protein gp120; D018696:Neuroprotective Agents; D004298:Dopamine