title: Simvastatin promotes adult hippocampal neurogenesis by enhancing Wnt/β-catenin signaling.
abstract: Statins improve recovery from traumatic brain injury and show promise in preventing Alzheimer disease. However, the mechanisms by which statins may be therapeutic for neurological conditions are not fully understood. In this study, we present the initial evidence that oral administration of simvastatin in mice enhances Wnt signaling in vivo. Concomitantly, simvastatin enhances neurogenesis in cultured adult neural progenitor cells as well as in the dentate gyrus of adult mice. Finally, we find that statins enhance Wnt signaling through regulation of isoprenoid synthesis and not through cholesterol. These findings provide direct evidence that Wnt signaling is enhanced in vivo by simvastatin and that this elevation of Wnt signaling is required for the neurogenic effects of simvastatin. Collectively, these data add to the growing body of evidence that statins may have therapeutic value for treating certain neurological disorders.
authors: University of Washington Department of Pharmacology, Seattle, WA 98195, USA ; Institute for Stem Cell and Regenerative Medicine, Seattle, WA 98109, USA ; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA ; University of Washington School of Medicine, Seattle, WA 98195, USA.
authors: Nicholas C
authors: NC
authors: Robin
authors: Institute for Stem Cell and Regenerative Medicine, Seattle, WA 98109, USA ; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA ; University of Washington School of Medicine, Seattle, WA 98195, USA.
authors: Zsuzsa
authors: Z
authors: Agoston
authors: University of Washington Department of Pharmacology, Seattle, WA 98195, USA ; Institute for Stem Cell and Regenerative Medicine, Seattle, WA 98109, USA ; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA ; University of Washington School of Medicine, Seattle, WA 98195, USA.
authors: Travis L
authors: TL
authors: Biechele
authors: Institute for Stem Cell and Regenerative Medicine, Seattle, WA 98109, USA ; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA ; University of Washington School of Medicine, Seattle, WA 98195, USA ; Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA 98101, USA.
authors: Richard G
authors: RG
authors: James
authors: Institute for Stem Cell and Regenerative Medicine, Seattle, WA 98109, USA ; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA ; University of Washington School of Medicine, Seattle, WA 98195, USA.
authors: Jason D
authors: JD
authors: Berndt
authors: University of Washington Department of Pharmacology, Seattle, WA 98195, USA ; Institute for Stem Cell and Regenerative Medicine, Seattle, WA 98109, USA ; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA ; University of Washington School of Medicine, Seattle, WA 98195, USA.
authors: Randall T
authors: RT
authors: Moon
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D051176:beta Catenin; D019821:Simvastatin; D006903:Hydroxymethylglutaryl CoA Reductases