Low-Dose Radiation Stimulates Wnt/β-Catenin Signaling, Neural Stem Cell Proliferation and Neurogenesis of the Mouse Hippocampus in vitro and in vivo

Author(s): Li-Chun Wei, Yin-Xiu Ding, Yong-Hong Liu, Li Duan, Ya Bai, Mei Shi, Liang-Wei Chen.

Journal Name: Current Alzheimer Research

Volume 9 , Issue 3 , 2012

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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, Wnt3aï¼ Œ 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 BrdUincorporation 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 highdose 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.

Keywords: Wnt signaling, neurogenesis, low-dose radiation, hippocampus, alzheimer’s disease

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Article Details

VOLUME: 9
ISSUE: 3
Year: 2012
Page: [278 - 289]
Pages: 12
DOI: 10.2174/156720512800107627
Price: $58

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