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.
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Research Article|
February 05 2021
Nasal Delivery of AntagomiR-741 Protects Against the Radiation-Induced Brain Injury in Mice
Mingqian Ou
;
Mingqian Ou
1
a Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
c Department of Neurology, Luoding People's Hospital, Affiliated Hospital of Guangdong Medical University, Luoding, China
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Weihao Fan
;
Weihao Fan
1
a Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
d Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
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Furong Sun
;
Furong Sun
1
a Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
d Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
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Minhua Li
;
Minhua Li
a Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
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Meijun Lin
;
Meijun Lin
a Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
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Yangsheng Yu
;
Yangsheng Yu
e Department of Neurology, Puning People's Hospital, Southern Medical University, Jieyang, China
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Shiyun Liang
;
Shiyun Liang
f Department of Otorhinolaryngology, Luoding People's Hospital, Affiliated Hospital of Guangdong Medical University, Luoding, China
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Haojie Liao
;
Haojie Liao
g Department of Neurology, Southern Medical University, Affiliated Shenzhen Bao An Hospital, Shenzhen, China
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Wanxin Jie
;
Wanxin Jie
a Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
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Yujie Cai
;
Yujie Cai
a Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
d Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
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Feng Chen
;
Feng Chen
a Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
d Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
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Xiongjin Chen
;
Xiongjin Chen
a Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
d Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
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Tian Zhao
;
Tian Zhao
b The Intensive Care Unit, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
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Pei Tang
;
Pei Tang
a Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
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Lili Cui
;
Lili Cui
2
a Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
d Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
2Address for correspondence: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Renmindadaonan 57th, Zhanjiang, China, 524000; e-mail: doctorzhh1201@126.com or cuilili@gdmu.edu.cn.
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Haihong Zhou
Haihong Zhou
2
a Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
d Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
2Address for correspondence: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Renmindadaonan 57th, Zhanjiang, China, 524000; e-mail: doctorzhh1201@126.com or cuilili@gdmu.edu.cn.
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Radiat Res (2021)
Article history
Received:
March 05 2020
Accepted:
December 09 2020
Citation
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; Nasal Delivery of AntagomiR-741 Protects Against the Radiation-Induced Brain Injury in Mice. Radiat Res 2021; doi: https://doi.org/10.1667/RADE-20-00070.1
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