PMID- 22815499 OWN - NLM STAT- MEDLINE DCOM- 20121024 LR - 20211021 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 32 IP - 29 DP - 2012 Jul 18 TI - Platelet-derived growth factor-BB restores human immunodeficiency virus Tat-cocaine-mediated impairment of neurogenesis: role of TRPC1 channels. PG - 9835-47 LID - 10.1523/JNEUROSCI.0638-12.2012 [doi] AB - Platelet-derived growth factor-BB (PDGF-BB) has been reported to provide tropic support for neurons in the CNS. However, whether PDGF-BB regulates neurogenesis, especially in the context of HIV-associated neurological disorder and drug abuse, remains essentially unknown. In this study, we demonstrate that pretreatment of rat hippocampal neuronal progenitor cells (NPCs) with PDGF-BB restored proliferation that had been impaired by HIV Tat-cocaine via the cognate receptors. We identify the essential role of transient receptor potential canonical (TRPC) channels in PDGF-BB-mediated proliferation. Parallel but distinct ERK/CREB, phosphatidylinositol 3-kinase/Akt signaling pathways with downstream activation of mammalian target of rapamycin (mTOR)/eukaryotic translation initiation factor 4E-binding protein (4E-BP)-p70S6K and nuclear factor-kappaB were critical for proliferation. Blocking TRPC1 channel suppressed PDGF-mediated proliferation as well as PDGF-BB-induced ERK/CREB and mTOR/4E-BP-p70S6K activation, thereby underscoring its role in this process. In vivo relevance of these findings was further corroborated in Tat transgenic mice wherein hippocampal injection of recombinant AAV2-PDGF-B restored impaired NPC proliferation that was induced by Tat-cocaine. Together, these data underpin the role of TRPC1 channel as a novel target that regulates cell proliferation mediated by PDGF-BB with implications for therapeutic intervention for reversal of impaired neurogenesis inflicted by Tat and cocaine. FAU - Yao, Honghong AU - Yao H AD - Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA. hyao@unmc.edu FAU - Duan, Ming AU - Duan M FAU - Yang, Lu AU - Yang L FAU - Buch, Shilpa AU - Buch S LA - eng GR - R01 DA024442/DA/NIDA NIH HHS/United States GR - R21 DA033614/DA/NIDA NIH HHS/United States GR - P30 MH062261/MH/NIMH NIH HHS/United States GR - DA 033150/DA/NIDA NIH HHS/United States GR - DA024442/DA/NIDA NIH HHS/United States GR - DA030285/DA/NIDA NIH HHS/United States GR - R21 DA030285/DA/NIDA NIH HHS/United States GR - R01 DA033150/DA/NIDA NIH HHS/United States GR - DA 033614/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Dopamine Uptake Inhibitors) RN - 0 (Proto-Oncogene Proteins c-sis) RN - 0 (TRPC Cation Channels) RN - 0 (tat Gene Products, Human Immunodeficiency Virus) RN - 0 (transient receptor potential cation channel, subfamily C, member 1) RN - 1B56C968OA (Becaplermin) RN - I5Y540LHVR (Cocaine) SB - IM MH - Animals MH - Becaplermin MH - Cell Proliferation/drug effects MH - Cocaine/*pharmacology MH - Dopamine Uptake Inhibitors/*pharmacology MH - Hippocampus/cytology/drug effects/metabolism MH - Neural Stem Cells/cytology/*drug effects/metabolism MH - Neurogenesis/*drug effects/physiology MH - Neurons/cytology/drug effects/metabolism MH - Proto-Oncogene Proteins c-sis/*pharmacology MH - RNA Interference MH - Rats MH - TRPC Cation Channels/genetics/*metabolism MH - tat Gene Products, Human Immunodeficiency Virus/*pharmacology PMC - PMC3438664 MID - NIHMS395457 EDAT- 2012/07/21 06:00 MHDA- 2012/10/25 06:00 PMCR- 2013/01/18 CRDT- 2012/07/21 06:00 PHST- 2012/07/21 06:00 [entrez] PHST- 2012/07/21 06:00 [pubmed] PHST- 2012/10/25 06:00 [medline] PHST- 2013/01/18 00:00 [pmc-release] AID - 32/29/9835 [pii] AID - 3787418 [pii] AID - 10.1523/JNEUROSCI.0638-12.2012 [doi] PST - ppublish SO - J Neurosci. 2012 Jul 18;32(29):9835-47. doi: 10.1523/JNEUROSCI.0638-12.2012.