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5 February 2021 Nasal Delivery of AntagomiR-741 Protects Against the Radiation-Induced Brain Injury in Mice
Mingqian Ou, Weihao Fan, Furong Sun, Minhua Li, Meijun Lin, Yangsheng Yu, Shiyun Liang, Haojie Liao, Wanxin Jie, Yujie Cai, Feng Chen, Xiongjin Chen, Tian Zhao, Pei Tang, Lili Cui, Haihong Zhou
Author Affiliations +
Abstract

Radiation-induced brain injury (RBI) is a serious complication in patients who have received radiotherapy for head and neck tumors. Currently, there is a scarcity of information on early diagnostic and preventive methods of RBI. Accumulating evidence suggests that microRNAs are involved in the regulation of radiation injury, but the molecular biological mechanism of miRNAs in RBI is largely unknown. Therefore, in our study, microRNA sequencing was used to discover differential miRNAs in the hippocampus of RBI-modeled mice, which suggested that miR-741-3p was most significantly upregulated. To clarify the underlying mechanism of miR-741-3p in RBI-modeled mice, an inhibitor of miR-741-3p (antagomiR-741) was delivered into the brain via the nasal passage before irradiation. The delivery of antagomiR-741 significantly reduced miR-741-3p levels in the hippocampus of RBI-modeled mice, and the cognitive dysfunction and neuronal apoptosis induced by radiation were also alleviated at 6 weeks postirradiation. Downregulation of miR-741-3p was found to improve the protrusion and branching status of microglia after irradiation and reduced the number of GFAP-positive astrocytes. Additionally, antagomiR-741 suppressed the radiation-induced production of pro-inflammatory cytokines IL-6 and TNF-α in the hippocampus and S100B in the serum. Furthermore, Ddr2, PKCα and St8sia1 were revealed as target genes of miR-741-3p and as potential regulatory targets for RBI. Overall, our study provides identification and functional evaluation of miRNA in RBI and lays the foundation for improving the prevention strategy for RBI based on the delivery of miRNA via the nose-brain pathway.

©2021 by Radiation Research Society. All rights of reproduction in any form reserved.
Mingqian Ou, Weihao Fan, Furong Sun, Minhua Li, Meijun Lin, Yangsheng Yu, Shiyun Liang, Haojie Liao, Wanxin Jie, Yujie Cai, Feng Chen, Xiongjin Chen, Tian Zhao, Pei Tang, Lili Cui, and Haihong Zhou "Nasal Delivery of AntagomiR-741 Protects Against the Radiation-Induced Brain Injury in Mice," Radiation Research 195(4), 355-365, (5 February 2021). https://doi.org/10.1667/RADE-20-00070.1
Received: 5 March 2020; Accepted: 9 December 2020; Published: 5 February 2021
JOURNAL ARTICLE
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