Inhibition of autophagy prevents irradiation-induced neural stem and progenitor cell death in the juvenile mouse brain.
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 autophagy might be a potential target for preventing radiotherapy-induced neural stem and progenitor cell death and its associated long-term side effects.
Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Department of Pediatrics, Zhengzhou Children's Hospital, Zhengzhou, China.
Yafeng
Y
Wang
Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Karolinska Institutet, Department of Women's and Children's Health, Karolinska University Hospital Q2:07, Stockholm, Sweden.
Kai
K
Zhou
Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Department of Pediatrics, Zhengzhou Children's Hospital, Zhengzhou, China.|Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Tao
T
Li
Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Yiran
Y
Xu
Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Cuicui
C
Xie
Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Yanyan
Y
Sun
Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Department of Pediatrics, Zhengzhou Children's Hospital, Zhengzhou, China.
Yaodong
Y
Zhang
Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Juan
J
Rodriguez
Karolinska Institutet, Department of Women's and Children's Health, Karolinska University Hospital Q2:07, Stockholm, Sweden.|Department of Pediatric Oncology, Karolinska University Hospital, Stockholm, Sweden.
Klas
K
Blomgren
Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Changlian
C
Zhu
D000818:Animals; D001343:Autophagy / Q000502:physiology* / Q000528:radiation effects; D016923:Cell Death / Q000502:physiology* / Q000528:radiation effects; D049109:Cell Proliferation / Q000502:physiology / Q000528:radiation effects; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D016207:Cytokines / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D011878:Radiotherapy / Q000009:adverse effects*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects
D016207:Cytokines