Low-dose radiation stimulates Wnt/β-catenin signaling, neural stem cell proliferation and neurogenesis of the mouse hippocampus in vitro and in vivo

Curr Alzheimer Res. 2012 Mar;9(3):278-89. doi: 10.2174/156720512800107627.

Abstract

Neurogenesis in the hippocampus is actively involved in neural circuit plasticity and learning function of mammals, but it may decrease dramatically with aging and aging-related neurodegenerative disorder Alzheimer's disease. Accumulating studies have indicated that Wnt/β-catenin signaling is critical in control of proliferation and differentiation fate of neural stem cells or progenitors in the hippocampus. In this study, the biological effects of low-dose radiation in stimulating Wnt/β-catenin signaling, neural stem cell proliferation and neurogenesis of hippocampus were interestingly identified by in vitro cell culture and in vivo animal studies. First, low-dose radiation (0.3Gy) induced significant increasing of Wnt1, Wnt3a, Wnt5a, and β-catenin expression in both neural stem cells and in situ hippocampus by immunohistochemical and PCR detection. Secondly, low-dose radiation enhanced the neurogenesis of hippocampus indicated by increasing proliferation and neuronal differentiation of neural stem cells, going up of nestin-expressing cells and BrdU-incorporation in hippocampus. Thirdly, it promoted cell survival and reduced apoptotic death of neuronal stem cells by flowcytometry analysis. Finally, Morris water-maze test showed behavioral improvement of animal learning in low-dose radiation group. Accordingly, detrimental influence on Wnt/β-catenin signaling or neurogenesis was confirmed in high-dose radiation (3.0Gy) group. Taken together, this study has revealed certain beneficial effects of low-dose radiation to stimulate neural stem cell proliferation, the neurogenesis of hippocampus and animal learning most possibly by triggering Wnt/β-catenin signaling cascades, suggesting its translational application role in devising new therapy for aging-related neurodegenerative disorders particularly Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / radiation effects*
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Hippocampus / radiation effects*
  • Mice
  • Mice, Inbred Strains
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / radiation effects*
  • Neurogenesis / physiology
  • Neurogenesis / radiation effects*
  • Primary Cell Culture
  • Spheroids, Cellular
  • Wnt Signaling Pathway / physiology
  • Wnt Signaling Pathway / radiation effects*
  • beta Catenin / metabolism
  • beta Catenin / radiation effects*

Substances

  • CTNNB1 protein, mouse
  • beta Catenin