title: Ionizing Radiation Perturbs Cell Cycle Progression of Neural Precursors in the Subventricular Zone Without Affecting Their Long-Term Self-Renewal.
abstract: Damage to normal human brain cells from exposure to ionizing radiation may occur during the course of radiotherapy or from accidental exposure. Delayed effects may complicate the immediate effects resulting in neurodegeneration and cognitive decline. We examined cellular and molecular changes associated with exposure of neural stem/progenitor cells (NSPs) to (137)Cs γ-ray doses in the range of 0 to 8 Gy. Subventricular zone NSPs isolated from newborn mouse pups were analyzed for proliferation, self-renewal, and differentiation, shortly after irradiation. Strikingly, there was no apparent increase in the fraction of dying cells after irradiation, and the number of single cells that formed neurospheres showed no significant change from control. Upon differentiation, irradiated neural precursors did not differ in their ability to generate neurons, astrocytes, and oligodendrocytes. By contrast, progression of NSPs through the cell cycle decreased dramatically after exposure to 8 Gy (p < .001). Mice at postnatal day 10 were exposed to 8 Gy of γ rays delivered to the whole body and NSPs of the subventricular zone were analyzed using a four-color flow cytometry panel combined with ethynyl deoxyuridine incorporation. Similar flow cytometric analyses were performed on NSPs cultured as neurospheres. These studies revealed that neither the percentage of neural stem cells nor their proliferation was affected. By contrast, γ-irradiation decreased the proliferation of two classes of multipotent cells and increased the proliferation of a specific glial-restricted precursor. Altogether, these results support the conclusion that primitive neural precursors are radioresistant, but their proliferation is slowed down as a consequence of γ-ray exposure.
authors.affiliation: Department of Neurology and Neurosciences, Rutgers University-New Jersey Medical School, Newark, NJ, USA.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Neurology and Neurosciences, Rutgers University-New Jersey Medical School, Newark, NJ, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Goodus
authors.affiliation: Department of Radiology, Rutgers University-New Jersey Medical School, Newark, NJ, USA.
authors.forename: Sonia M
authors.initials: SM
authors.lastname: de Toledo
authors.affiliation: Department of Radiology, Rutgers University-New Jersey Medical School, Newark, NJ, USA.
authors.forename: Edouard I
authors.initials: EI
authors.lastname: Azzam
authors.affiliation: Department of Neurology and Neurosciences, Rutgers University-New Jersey Medical School, Newark, NJ, USA.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Levison
authors.affiliation: Department of Neurology and Neurosciences, Rutgers University-New Jersey Medical School, Newark, NJ, USA souayani@njms.rutgers.edu.
authors.forename: Nizar
authors.initials: N
authors.lastname: Souayah
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000502:physiology / Q000528:radiation effects; D001921:Brain / Q000502:physiology / Q000528:radiation effects*; D059447:Cell Cycle Checkpoints / Q000502:physiology / Q000528:radiation effects; D000066673:Cell Self Renewal / Q000502:physiology / Q000528:radiation effects*; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects; D002478:Cells, Cultured; D002588:Cesium Radioisotopes / Q000009:adverse effects*; D005720:Gamma Rays / Q000009:adverse effects*; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000502:physiology / Q000528:radiation effects*; D055495:Neurogenesis / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000502:physiology / Q000528:radiation effects; D009836:Oligodendroglia / Q000502:physiology / Q000528:radiation effects; D055153:Stem Cell Niche / Q000502:physiology / Q000528:radiation effects*
chemical_list: D002588:Cesium Radioisotopes
keywords: brain; cancer; cell death; cell differentiation; radiation-induced cell cycle checkpoints; stem cells