Simvastatin promotes adult hippocampal neurogenesis by enhancing Wnt/β-catenin signaling

Stem Cell Reports. 2013 Dec 26;2(1):9-17. doi: 10.1016/j.stemcr.2013.11.002. eCollection 2014 Jan 14.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Hippocampus / cytology*
  • Hippocampus / metabolism
  • Hydroxymethylglutaryl CoA Reductases / chemistry
  • Hydroxymethylglutaryl CoA Reductases / genetics
  • Hydroxymethylglutaryl CoA Reductases / metabolism
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neurogenesis / drug effects*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Simvastatin / pharmacology*
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway / drug effects*
  • beta Catenin / metabolism

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • RNA, Small Interfering
  • Wnt Proteins
  • beta Catenin
  • Simvastatin
  • Hydroxymethylglutaryl CoA Reductases