Sildenafil enhances neurogenesis and oligodendrogenesis in ischemic brain of middle-aged mouse

• Published in: PloS one Vol. 7; no. 10; p. e48141
• Main Authors: Zhang, Rui Lan, Chopp, Michael, Roberts, Cynthia, Wei, Min, Wang, Xinli, Liu, Xianshuang, Lu, Mei, Zhang, Zheng Gang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.10.2012; Public Library of Science (PLoS)
• Subjects: Adenomatous polyposis coli; Aging; Angiogenesis; Animals; Astrocytes; Bacterial Proteins - biosynthesis; Bacterial Proteins - genetics; Biology; Brain; Cell Tracking; Corpus callosum; Corpus Callosum - drug effects; Corpus Callosum - metabolism; Corpus Callosum - pathology; DNA-Binding Proteins; Fluorescence; Growth factors; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - pathology; Intermediate filament proteins; Intermediate Filament Proteins - metabolism; Ischemia; Lateral Ventricles - drug effects; Lateral Ventricles - metabolism; Lateral Ventricles - pathology; Luminescent Proteins - biosynthesis; Luminescent Proteins - genetics; Male; Medicine; Mice; Mice, Transgenic; Middle age; Neostriatum; Nerve Tissue Proteins - metabolism; Nestin; Neural stem cells; Neural Stem Cells - drug effects; Neural Stem Cells - metabolism; Neural Stem Cells - physiology; Neurogenesis; Neurogenesis - drug effects; Neurology; Neurons; Nuclear Proteins - metabolism; Oligodendrocytes; Oligodendroglia - drug effects; Oligodendroglia - metabolism; Oligodendroglia - physiology; Phosphodiesterase; Phosphodiesterase 5 Inhibitors - pharmacology; Phosphodiesterase 5 Inhibitors - therapeutic use; Piperazines - pharmacology; Piperazines - therapeutic use; Polyposis coli; Progeny; Purines - pharmacology; Purines - therapeutic use; Rodents; Sildenafil; Sildenafil Citrate; Stem cell transplantation; Stem cells; Stroke; Subventricular zone; Sulfones - pharmacology; Sulfones - therapeutic use; Ventricle (lateral); Yellow fluorescent protein; Detroit Michigan; United States > US; Michigan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0048141

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.