AUTHOR=Wang Yafeng , Zhou Kai , Li Tao , Xu Yiran , Xie Cuicui , Sun Yanyan , Rodriguez Juan , Zhang Shan , Song Juan , Wang Xiaoyang , Blomgren Klas , Zhu Changlian 

TITLE=Selective Neural Deletion of the Atg7 Gene Reduces Irradiation-Induced Cerebellar White Matter Injury in the Juvenile Mouse Brain by Ameliorating Oligodendrocyte Progenitor Cell Loss

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=13

YEAR=2019

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2019.00241

DOI=10.3389/fncel.2019.00241

ISSN=1662-5102

ABSTRACT=<p>Radiotherapy is an effective tool for treating brain tumors, but irradiation-induced toxicity to the normal brain tissue remains a major problem. Here, we investigated if selective neural <italic>autophagy related gene 7</italic> (<italic>Atg7</italic>) deletion has a persistent effect on irradiation-induced juvenile mouse brain injury. Ten-day-old <italic>Atg7</italic> knockout under a nestin promoter (KO) mice and wild-type (WT) littermates were subjected to a single dose of 6 Gy whole-brain irradiation. Cerebellar volume, cell proliferation, microglia activation, inflammation, and myelination were evaluated in the cerebellum at 5 days after irradiation. We found that neural <italic>Atg7</italic> deficiency partially prevented myelin disruption compared to the WT mice after irradiation, as indicated by myelin basic protein staining. Irradiation induced oligodendrocyte progenitor cell (OPC) loss in the white matter of the cerebellum, and <italic>Atg7</italic> deficiency partly prevented this. The mRNA expression of oligodendrocyte and myelination-related genes (<italic>Olig2</italic>, <italic>Cldn11</italic>, <italic>CNP</italic>, and <italic>MBP</italic>) was higher in the cerebellum in <italic>Atg7</italic> KO mice compared with WT littermates. The total cerebellar volume was significantly reduced after irradiation in both <italic>Atg7</italic> KO and WT mice. <italic>Atg7</italic>-deficient cerebellums were in a regenerative state before irradiation, as judged by the increased OPC-related and neurogenesis-related transcripts and the increased numbers of microglia; however, except for the OPC parameters these were the same in both genotypes after irradiation. Finally, there was no significant change in the number of astrocytes in the cerebellum after irradiation. These results suggest that selective neural <italic>Atg7</italic> deficiency reduces irradiation-induced cerebellar white matter injury in the juvenile mouse brain, secondary to prevention of OPC loss.</p>