Abstract:
:The prevalence of central nervous system (CNS) neurologic dysfunction associated with human immunodeficiency virus (HIV) infection continues to increase, despite the use of antiretroviral therapy. Previous work has focused on the deleterious effects of HIV on mature neurons and on development of neuroprotective strategies, which have consistently failed to show a meaningful clinical benefit. It is now well established that new neurons are continuously generated in discrete regions in the adult mammalian brain, and accumulating evidence supports important roles for these neurons in specific cognitive functions. In a transgenic mouse model of HIV neurologic disease with glial expression of the HIV envelope protein gp120, we demonstrate a significant reduction in proliferation of hippocampal neural progenitors in the dentate gyrus of adult animals, resulting in a dramatic decrease in the number of newborn neurons in the adult brain. We identify amplifying neural progenitor cells (ANPs) as the first class of progenitors affected by gp120, and we also demonstrate that newly generated neurons exhibit aberrant dendritic development. Furthermore, voluntary exercise and treatment with a selective serotonin reuptake inhibitor increase the ANP population and rescue the observed deficits in gp120 transgenic mice. Thus, during HIV infection, the envelope protein gp120 may potently inhibit adult hippocampal neurogenesis, and neurorestorative approaches may be effective in ameliorating these effects. Our study has significant implications for the development of novel therapeutic approaches for HIV-infected individuals with neurologic dysfunction and may be applicable to other neurodegenerative diseases in which hippocampal neurogenesis is impaired.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Lee MH,Wang T,Jang MH,Steiner J,Haughey N,Ming GL,Song H,Nath A,Venkatesan Adoi
10.1016/j.nbd.2010.12.002subject
Has Abstractpub_date
2011-03-01 00:00:00pages
678-87issue
3eissn
0969-9961issn
1095-953Xpii
S0969-9961(10)00395-5journal_volume
41pub_type
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