PMID- 23982957 OWN - NLM STAT- MEDLINE DCOM- 20140507 LR - 20240216 IS - 1538-2443 (Electronic) IS - 1355-0284 (Print) IS - 1355-0284 (Linking) VI - 19 IP - 5 DP - 2013 Oct TI - Impaired neurogenesis and neurite outgrowth in an HIV-gp120 transgenic model is reversed by exercise via BDNF production and Cdk5 regulation. PG - 418-31 LID - 10.1007/s13365-013-0194-6 [doi] AB - 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. FAU - Lee, Myoung-Hwa AU - Lee MH AD - 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. FAU - Amin, Niranjana D AU - Amin ND FAU - Venkatesan, Arun AU - Venkatesan A FAU - Wang, Tongguang AU - Wang T FAU - Tyagi, Richa AU - Tyagi R FAU - Pant, Harish C AU - Pant HC FAU - Nath, Avindra AU - Nath A LA - eng GR - R01 DA024593/DA/NIDA NIH HHS/United States GR - ZIA NS003130-02/Intramural NIH HHS/United States GR - R01 NS039253/NS/NINDS NIH HHS/United States GR - R01-NS039253/NS/NINDS NIH HHS/United States GR - R01-DA024593/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural DEP - 20130827 PL - United States TA - J Neurovirol JT - Journal of neurovirology JID - 9508123 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (HIV Envelope Protein gp120) RN - 147336-22-9 (Green Fluorescent Proteins) RN - EC 2.7.11.1 (Cyclin-Dependent Kinase 5) RN - EC 2.7.11.22 (Cdk5 protein, mouse) SB - IM CIN - J Neurovirol. 2013 Oct;19(5):407-9. PMID: 24072548 MH - AIDS Dementia Complex/*genetics/metabolism/pathology MH - Animals MH - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics MH - Cell Proliferation MH - Cell Survival MH - Cyclin-Dependent Kinase 5/*genetics/metabolism MH - Dentate Gyrus/metabolism/pathology MH - Disease Models, Animal MH - Gene Expression Regulation MH - Genes, Reporter MH - Green Fluorescent Proteins/genetics MH - HIV Envelope Protein gp120/*genetics/metabolism MH - Humans MH - Male MH - Mice MH - Mice, Transgenic MH - Neurites/*metabolism/pathology MH - Neurogenesis/genetics MH - *Physical Conditioning, Animal MH - Transgenes PMC - PMC3799978 MID - NIHMS519669 COIS- Conflict of interest The authors declare that they have no conflict of interest. EDAT- 2013/08/29 06:00 MHDA- 2014/05/08 06:00 PMCR- 2014/10/01 CRDT- 2013/08/29 06:00 PHST- 2013/07/18 00:00 [received] PHST- 2013/07/31 00:00 [accepted] PHST- 2013/08/29 06:00 [entrez] PHST- 2013/08/29 06:00 [pubmed] PHST- 2014/05/08 06:00 [medline] PHST- 2014/10/01 00:00 [pmc-release] AID - 10.1007/s13365-013-0194-6 [doi] PST - ppublish SO - J Neurovirol. 2013 Oct;19(5):418-31. doi: 10.1007/s13365-013-0194-6. Epub 2013 Aug 27.