title: Sildenafil enhances neurogenesis and oligodendrogenesis in ischemic brain of middle-aged mouse.
abstract: Adult neural stem cells give rise to neurons, oligodendrocytes and astrocytes. Aging reduces neural stem cells. Using an inducible nestin-CreER(T2)/R26R-yellow fluorescent protein (YFP) mouse, we investigated the effect of Sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, on nestin lineage neural stem cells and their progeny in the ischemic brain of the middle-aged mouse. We showed that focal cerebral ischemia induced nestin lineage neural stem cells in the subventricular zone (SVZ) of the lateral ventricles and nestin expressing NeuN positive neurons and adenomatous polyposis coli (APC) positive mature oligodendrocytes in the ischemic striatum and corpus callosum in the aged mouse. Treatment of the ischemic middle-aged mouse with Sildenafil increased nestin expressing neural stem cells, mature neurons, and oligodendrocytes by 33, 75, and 30%, respectively, in the ischemic brain. These data indicate that Sildenafil amplifies nestin expressing neural stem cells and their neuronal and oligodendrocyte progeny in the ischemic brain of the middle-aged mouse.
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, Michigan, USA.
authors.forename: Rui Lan
authors.initials: RL
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
authors.forename: Cynthia
authors.initials: C
authors.lastname: Roberts
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Xinli
authors.initials: X
authors.lastname: Wang
authors.forename: Xianshuang
authors.initials: X
authors.lastname: Liu
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: Zheng Gang
authors.initials: ZG
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D058948:Cell Tracking; D003337:Corpus Callosum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D007381:Intermediate Filament Proteins / Q000378:metabolism; D020547:Lateral Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects*; D009687:Nuclear Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D007381:Intermediate Filament Proteins; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; C054562:yellow fluorescent protein, Bacteria; D000068677:Sildenafil Citrate