Dataset Information

Grafting Neural Stem and Progenitor Cells Into the Hippocampus of Juvenile, Irradiated Mice Normalizes Behavior Deficits.

ABSTRACT: The pool of neural stem and progenitor cells (NSPCs) in the dentate gyrus of the hippocampus is reduced by ionizing radiation. This explains, at least partly, the learning deficits observed in patients after radiotherapy, particularly in pediatric cases. An 8 Gy single irradiation dose was delivered to the whole brains of postnatal day 9 (P9) C57BL/6 mice, and BrdU-labeled, syngeneic NSPCs (1.0 × 10⁵ cells/injection) were grafted into each hippocampus on P21. Three months later, behavior tests were performed. Irradiation impaired novelty-induced exploration, place learning, reversal learning, and sugar preference, and it altered the movement pattern. Grafting of NSPCs ameliorated or even normalized the observed deficits. Less than 4% of grafted cells survived and were found in the dentate gyrus 5 months later. The irradiation-induced loss of endogenous, undifferentiated NSPCs in the dentate gyrus was completely restored by grafted NSPCs in the dorsal, but not the ventral, blade. The grafted NSPCs did not exert appreciable effects on the endogenous NSPCs; however, more than half of the grafted NSPCs differentiated. These results point to novel strategies aimed at ameliorating the debilitating late effects of cranial radiotherapy, particularly in children.

SUBMITTER: Sato Y

PROVIDER: S-EPMC6141740 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Grafting Neural Stem and Progenitor Cells Into the Hippocampus of Juvenile, Irradiated Mice Normalizes Behavior Deficits.

Sato Yoshiaki Y Shinjyo Noriko N Sato Machiko M Nilsson Marie K L MKL Osato Kazuhiro K Zhu Changlian C Pekna Marcela M Kuhn Hans G HG Blomgren Klas K

Frontiers in neurology 20180911

The pool of neural stem and progenitor cells (NSPCs) in the dentate gyrus of the hippocampus is reduced by ionizing radiation. This explains, at least partly, the learning deficits observed in patients after radiotherapy, particularly in pediatric cases. An 8 Gy single irradiation dose was delivered to the whole brains of postnatal day 9 (P9) C57BL/6 mice, and BrdU-labeled, syngeneic NSPCs (1.0 × 10<sup>5</sup> cells/injection) were grafted into each hippocampus on P21. Three months later, behav ...[more]

PMID: 30254600

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Project description:While irradiation can effectively treat brain tumors, this therapy also causes cognitive impairments, some of which may stem from the disruption of hippocampal neurogenesis. To study how radiation affects neurogenesis, we combine phenotyping of subpopulations of hippocampal neural stem and progenitor cells with double- and triple S-phase labeling paradigms. Using this approach, we reveal new features of division, survival, and differentiation of neural stem and progenitor cells after exposure to gamma radiation. We show that dividing neural stem cells, while susceptible to damage induced by gamma rays, are less vulnerable than their rapidly amplifying progeny. We also show that dividing stem and progenitor cells that survive irradiation are suppressed in their ability to replicate 0.5-1 day after the radiation exposure. Suppression of division is also observed for cells that entered the cell cycle after irradiation or were not in the S phase at the time of exposure. Determining the longer term effects of irradiation, we found that 2 months after exposure, radiation-induced suppression of division is partially relieved for both stem and progenitor cells, without evidence for compensatory symmetric divisions as a means to restore the normal level of neurogenesis. By that time, most mature young neurons, born 2-4 weeks after the irradiation, still bear the consequences of radiation exposure, unlike younger neurons undergoing early stages of differentiation without overt signs of deficient maturation. Later, 6 months after an exposure to 5 Gy, cell proliferation and neurogenesis are further impaired, though neural stem cells are still available in the niche, and their pool is preserved. Our results indicate that various subpopulations of stem and progenitor cells in the adult hippocampus have different susceptibility to gamma radiation, and that neurogenesis, even after a temporary restoration, is impaired in the long term after exposure to gamma rays. Our study provides a framework for investigating critical issues of neural stem cell maintenance, aging, interaction with their microenvironment, and post-irradiation therapy.

Dataset Information

Grafting Neural Stem and Progenitor Cells Into the Hippocampus of Juvenile, Irradiated Mice Normalizes Behavior Deficits.

Publications

Grafting Neural Stem and Progenitor Cells Into the Hippocampus of Juvenile, Irradiated Mice Normalizes Behavior Deficits.

Similar Datasets

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