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Inhibition of autophagy prevents irradiation-induced neural stem and progenitor cell death in the juvenile mouse brain

Artikel i vetenskaplig tidskrift
Författare Yafeng Wang
Kai Zhou
Tao Li
Yiran Xu
Cuicui Xie
Yanyan Sun
Yaodong Zhang
Juan Rodriguez
K. Blomgren
Changlian Zhu
Publicerad i Cell Death & Disease
Volym 8
ISSN 2041-4889
Publiceringsår 2017
Publicerad vid Institutionen för neurovetenskap och fysiologi
Språk en
Länkar doi.org/10.1038/cddis.2017.120
Ämnesord central-nervous-system, ionizing-radiation, hypoxia-ischemia, long-term, hippocampal neurogenesis, microglia activation, subventricular zone, dentate gyrus, glioma-cells, apoptosis, Cell Biology
Ämneskategorier Cellbiologi

Sammanfattning

Radiotherapy is an effective tool in the treatment of malignant brain tumors. However, damage to brain stem and progenitor cells constitutes a major problem and is associated with long-term side effects. Autophagy has been shown to be involved in cell death, and the purpose of this study was to evaluate the effect of autophagy inhibition on neural stem and progenitor cell death in the juvenile brain. Ten-day-old selective Atg7 knockout (KO) mice and wild-type (WT) littermates were subjected to a single 6Gy dose of whole-brain irradiation. Cell death and proliferation as well as microglia activation and inflammation were evaluated in the dentate gyrus of the hippocampus and in the cerebellum at 6 h after irradiation. We found that cell death was reduced in Atg7 KO compared with WT mice at 6 h after irradiation. The number of activated microglia increased significantly in both the dentate gyrus and the cerebellum of WT mice after irradiation, but the increase was lower in the Atg7 KO mice. The levels of proinflammatory cytokines and chemokines decreased, especially in the cerebellum, in the Atg7 KO group. These results suggest that autophagymight be a potential target for preventing radiotherapy-induced neural stem and progenitor cell death and its associated long-term side effects.

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