title: Low-dose radiation stimulates Wnt/β-catenin signaling, neural stem cell proliferation and neurogenesis of the mouse hippocampus in vitro and in vivo.
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.
authors.affiliation: Department of Radiation Oncology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Wei
authors.forename: Yin-Xiu
authors.initials: YX
authors.lastname: Ding
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Duan
authors.forename: Ya
authors.initials: Y
authors.lastname: Bai
authors.forename: Mei
authors.initials: M
authors.lastname: Shi
authors.forename: Liang-Wei
authors.initials: LW
authors.lastname: Chen
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000528:radiation effects*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D008815:Mice, Inbred Strains; D058953:Neural Stem Cells / Q000378:metabolism / Q000528:radiation effects*; D055495:Neurogenesis / Q000502:physiology / Q000528:radiation effects*; D061251:Primary Cell Culture; D018874:Spheroids, Cellular; D060449:Wnt Signaling Pathway / Q000502:physiology / Q000528:radiation effects*; D051176:beta Catenin / Q000378:metabolism / Q000528:radiation effects*
chemical_list: C495267:CTNNB1 protein, mouse; D051176:beta Catenin