title: Impaired neurogenesis and neurite outgrowth in an HIV-gp120 transgenic model is reversed by exercise via BDNF production and Cdk5 regulation.
abstract: Human immunodeficiency virus (HIV) infection-associated neurocognitive disorders is accompanied with brain atrophy. In these patients, impairment of adult neurogenesis and neurite outgrowth in the hippocampus may contribute to cognitive dysfunction. Although running exercises can enhance neurogenesis and normalize neurite outgrowth, the underlying molecular mechanisms are not well understood. The HIV envelope protein, gp120, has been shown to impair neurogenesis. Using a gp120 transgenic mouse model, we demonstrate that exercise stimulated neural progenitor cell (NPC) proliferation in the hippocampal dentate gyrus and increased the survival rate and generation of newborn cells. However, sustained exercise activity was necessary as the effects were reversed by detraining. Exercise also normalized dendritic outgrowth of neurons. Furthermore, it increased the expression of hippocampal brain-derived neurotrophic factor (BDNF) and normalized hyperactivation of cyclin-dependent kinase 5 (Cdk5). Hyperactivated Cdk5 or gp120 treatment led to aberrant neurite outgrowth and BDNF treatment normalized the neurite outgrowth in NPC cultures. These results suggest that sustained exercise has trophic activity on the neuronal lineage which is mediated by Cdk5 modulation of the BDNF pathway.
authors: Section of Infections of the Nervous System, National Institutes of Health, M.D. Bldg 10, Room 7C-103, 10 Center Drive, Bethesda, MD, 20892, USA.
authors: Myoung-Hwa
authors: MH
authors: Lee
authors: Niranjana D
authors: ND
authors: Amin
authors: Arun
authors: A
authors: Venkatesan
authors: Tongguang
authors: T
authors: Wang
authors: Richa
authors: R
authors: Tyagi
authors: Harish C
authors: HC
authors: Pant
authors: Avindra
authors: A
authors: Nath
mesh_terms: D015526:AIDS Dementia Complex / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics* / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016501:Neurites / Q000378:metabolism* / Q000473:pathology; D055495:Neurogenesis / Q000235:genetics; D010805:Physical Conditioning, Animal; D019076:Transgenes
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015699:HIV Envelope Protein gp120; D049452:Green Fluorescent Proteins; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse
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