Intranasal Administration of miR-146a Agomir Rescued the Pathological Process and Cognitive Impairment in an AD Mouse Model
Alzheimer’s disease (AD) is the most common cause of dementia and cannot be cured. The etiology and pathogenesis of AD is still not fully understood, the genetics is considered to be one of the most important factors for AD onset, and the identified susceptible genes could provide clues to the AD me...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-12-01
|
| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S216225311930277X |
| id |
doaj-2490e1732fd547818bf4c6e166dc552f |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Hui Mai Weihao Fan Yan Wang Yujie Cai Xiaohui Li Feng Chen Xiongjin Chen Jingqi Yang Pei Tang Huiyi Chen Ting Zou Tingting Hong Conghua Wan Bin Zhao Lili Cui |
| spellingShingle |
Hui Mai Weihao Fan Yan Wang Yujie Cai Xiaohui Li Feng Chen Xiongjin Chen Jingqi Yang Pei Tang Huiyi Chen Ting Zou Tingting Hong Conghua Wan Bin Zhao Lili Cui Intranasal Administration of miR-146a Agomir Rescued the Pathological Process and Cognitive Impairment in an AD Mouse Model Molecular Therapy: Nucleic Acids |
| author_facet |
Hui Mai Weihao Fan Yan Wang Yujie Cai Xiaohui Li Feng Chen Xiongjin Chen Jingqi Yang Pei Tang Huiyi Chen Ting Zou Tingting Hong Conghua Wan Bin Zhao Lili Cui |
| author_sort |
Hui Mai |
| title |
Intranasal Administration of miR-146a Agomir Rescued the Pathological Process and Cognitive Impairment in an AD Mouse Model |
| title_short |
Intranasal Administration of miR-146a Agomir Rescued the Pathological Process and Cognitive Impairment in an AD Mouse Model |
| title_full |
Intranasal Administration of miR-146a Agomir Rescued the Pathological Process and Cognitive Impairment in an AD Mouse Model |
| title_fullStr |
Intranasal Administration of miR-146a Agomir Rescued the Pathological Process and Cognitive Impairment in an AD Mouse Model |
| title_full_unstemmed |
Intranasal Administration of miR-146a Agomir Rescued the Pathological Process and Cognitive Impairment in an AD Mouse Model |
| title_sort |
intranasal administration of mir-146a agomir rescued the pathological process and cognitive impairment in an ad mouse model |
| publisher |
Elsevier |
| series |
Molecular Therapy: Nucleic Acids |
| issn |
2162-2531 |
| publishDate |
2019-12-01 |
| description |
Alzheimer’s disease (AD) is the most common cause of dementia and cannot be cured. The etiology and pathogenesis of AD is still not fully understood, the genetics is considered to be one of the most important factors for AD onset, and the identified susceptible genes could provide clues to the AD mechanism and also be the potential targets. MicroRNA-146a-5p (miR-146a) is well known in the regulation of the inflammatory response, and the functional SNP of miR-146a was associated with AD risk. In this study, using a noninvasive nasal administration, we discovered that a miR-146a agomir (M146AG) rescued cognitive impairment in the APP/PS1 transgenic mouse and alleviated the overall pathological process in the AD mouse model, including neuroinflammation, glia activation, Aβ deposit, and tau phosphorylation in hippocampi. Furthermore, the transcriptional analysis revealed that besides the effect of neuroinflammation, M146AG may serve as a multi-potency target for intervention in AD. In addition, Srsf6 was identified as a target of miR-146a, which may play a role in AD progression. In conclusion, our study supports that the nasal-to-brain pathway is efficient and operable for the brain administration of microRNAs (miRNAs), and that miR-146a may be a new potential target for AD treatment. Keywords: miR-146a-5p, Alzheimer’s disease, intranasal administration, srsf6, neuroinflammation |
| url |
http://www.sciencedirect.com/science/article/pii/S216225311930277X |
| work_keys_str_mv |
AT huimai intranasaladministrationofmir146aagomirrescuedthepathologicalprocessandcognitiveimpairmentinanadmousemodel AT weihaofan intranasaladministrationofmir146aagomirrescuedthepathologicalprocessandcognitiveimpairmentinanadmousemodel AT yanwang intranasaladministrationofmir146aagomirrescuedthepathologicalprocessandcognitiveimpairmentinanadmousemodel AT yujiecai intranasaladministrationofmir146aagomirrescuedthepathologicalprocessandcognitiveimpairmentinanadmousemodel AT xiaohuili intranasaladministrationofmir146aagomirrescuedthepathologicalprocessandcognitiveimpairmentinanadmousemodel AT fengchen intranasaladministrationofmir146aagomirrescuedthepathologicalprocessandcognitiveimpairmentinanadmousemodel AT xiongjinchen intranasaladministrationofmir146aagomirrescuedthepathologicalprocessandcognitiveimpairmentinanadmousemodel AT jingqiyang intranasaladministrationofmir146aagomirrescuedthepathologicalprocessandcognitiveimpairmentinanadmousemodel AT peitang intranasaladministrationofmir146aagomirrescuedthepathologicalprocessandcognitiveimpairmentinanadmousemodel AT huiyichen intranasaladministrationofmir146aagomirrescuedthepathologicalprocessandcognitiveimpairmentinanadmousemodel AT tingzou intranasaladministrationofmir146aagomirrescuedthepathologicalprocessandcognitiveimpairmentinanadmousemodel AT tingtinghong intranasaladministrationofmir146aagomirrescuedthepathologicalprocessandcognitiveimpairmentinanadmousemodel AT conghuawan intranasaladministrationofmir146aagomirrescuedthepathologicalprocessandcognitiveimpairmentinanadmousemodel AT binzhao intranasaladministrationofmir146aagomirrescuedthepathologicalprocessandcognitiveimpairmentinanadmousemodel AT lilicui intranasaladministrationofmir146aagomirrescuedthepathologicalprocessandcognitiveimpairmentinanadmousemodel |
| _version_ |
1725058233811337216 |
| spelling |
doaj-2490e1732fd547818bf4c6e166dc552f2020-11-25T01:37:20ZengElsevierMolecular Therapy: Nucleic Acids2162-25312019-12-0118681695Intranasal Administration of miR-146a Agomir Rescued the Pathological Process and Cognitive Impairment in an AD Mouse ModelHui Mai0Weihao Fan1Yan Wang2Yujie Cai3Xiaohui Li4Feng Chen5Xiongjin Chen6Jingqi Yang7Pei Tang8Huiyi Chen9Ting Zou10Tingting Hong11Conghua Wan12Bin Zhao13Lili Cui14Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China; Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China; Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaGuangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaSchool of Humanities and Management, Research Center for Quality of Life and Applied Psychology, Guangdong Medical University, Dongguan, China; Corresponding author: Conghua Wan, School of Humanities and Management, Research Center for Quality of Life and Applied Psychology, Guangdong Medical University, Dongguan, China.Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China; Corresponding author: Bin Zhao, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China; Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China; Corresponding author: Lili Cui, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.Alzheimer’s disease (AD) is the most common cause of dementia and cannot be cured. The etiology and pathogenesis of AD is still not fully understood, the genetics is considered to be one of the most important factors for AD onset, and the identified susceptible genes could provide clues to the AD mechanism and also be the potential targets. MicroRNA-146a-5p (miR-146a) is well known in the regulation of the inflammatory response, and the functional SNP of miR-146a was associated with AD risk. In this study, using a noninvasive nasal administration, we discovered that a miR-146a agomir (M146AG) rescued cognitive impairment in the APP/PS1 transgenic mouse and alleviated the overall pathological process in the AD mouse model, including neuroinflammation, glia activation, Aβ deposit, and tau phosphorylation in hippocampi. Furthermore, the transcriptional analysis revealed that besides the effect of neuroinflammation, M146AG may serve as a multi-potency target for intervention in AD. In addition, Srsf6 was identified as a target of miR-146a, which may play a role in AD progression. In conclusion, our study supports that the nasal-to-brain pathway is efficient and operable for the brain administration of microRNAs (miRNAs), and that miR-146a may be a new potential target for AD treatment. Keywords: miR-146a-5p, Alzheimer’s disease, intranasal administration, srsf6, neuroinflammationhttp://www.sciencedirect.com/science/article/pii/S216225311930277X |