Ghrelin modulates dopaminergic neuron formation and attention deficit hyperactivity disorder-like behaviors: From animals to human models

doi:10.1016/j.bbi.2020.12.029

科研成果详情

题名	Ghrelin modulates dopaminergic neuron formation and attention deficit hyperactivity disorder-like behaviors: From animals to human models
作者	Shi, Xulai1; Guan, Kaiyu 1; Peng, Xuyan 2; Xu, Bingru 3; Zhou, Xianyong 1; Wang, Shao 1; Xu, Shengnan 1; Zheng, Miaomiao 1; Huang, Jing 4; Wan, Xiaoyang 5; Guan, Wanchun3; Su, Kuan-Pin 6,7; Ye, Minjie1; Gao, Xiang 8; Yin, Zhan 2; Li, Xi1
发表日期	2021-05
发表期刊	BRAIN BEHAVIOR AND IMMUNITY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Attention deficiency Ghrelin Hyperactivity Zebrafish Dopaminergic neuron
其他关键词	STIMULATES LOCOMOTOR-ACTIVITY ; DEFICIT/HYPERACTIVITY DISORDER ; ZEBRAFISH ; MEMORY ; ADHD ; INCREASES ; NUCLEUS ; GENE ; RESPONSES ; SUBTYPES
摘要	Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in children. The orexigenic hormone ghrelin is important in neuroprotection and neurodevelopment, which may play an important role in psychopathogenesis of ADHD. This study aimed to systematically investigate the genomic and pharmacological manipulations of ghrelin functioning in ADHD-like symptoms in zebrafish models and validated the effects of ghrelin polymorphisms in human subjects with ADHD. We firstly generated ghrelin?/? zebrafish mutant, which displayed hyperactive, attention deficit-like and impulsive-like behaviors, as well as endophenotypes, mimicking human ADHD. Ghrelin?/? zebrafish exhibited downregulated expression levels of wnt1, wnt3a, wnt5a that are critical for dopaminergic neuron development to possibly regulate their number and spatial organization. Pharmacological blockade of wnt signaling with XAV939 induced a reduced moving activity and less dopaminergic neurons; whereas, wnt agonist SB415286 rescued hyperactivity and dopaminergic neuron loss in ghrelin?/? zebrafish. In addition, we further identified and validated a SNP, rs696217, on orexigenic hormone preproghrelin/ghrelin (T408T, Met72Met) to be associated with a higher risk of ADHD in a case-controlled association study with 248 subjects with ADHD and 208 subjects of healthy controls. Together, our results reveal a novel endogenous role for orexigenic hormone ghrelin in ADHD, which provides insights into genetic regulation and drug screens for the identification of novel treatments of ADHD.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31530077, 31802314]; Natural Science Foundation of Hubei ProvinceNatural Science Foundation of Hubei Province [2020CFB737]; Wenzhou Municipal Sci-Tech Bureau Program [Y20170017, Y20180489]; China Medical UniversityChina Medical University [CMU104-S-16-01, CMU103-BC-4-1, DMR-109102, DMR-109-244, DMR-HHC-109-11, DMR-HCC-109-12]
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
出版地	SAN DIEGO
ISSN	0889-1591
EISSN	1090-2139
卷号	94 页码:327-337
DOI	10.1016/j.bbi.2020.12.029
页数	11
WOS类目	Immunology ; Neurosciences ; Psychiatry
WOS研究方向	Immunology ; Neurosciences & Neurology ; Psychiatry
WOS记录号	WOS:000640700200011
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	33412253
SCOPUSEID	2-s2.0-85101078478
通讯作者地址	[Gao, Xiang]The Affiliated Kangning Hospital of Wenzhou Medical University,1 Shengjin Road,Lucheng,325000,China
Scopus学科分类	Immunology;Endocrine and Autonomic Systems;Behavioral Neuroscience
TOP期刊	TOP期刊
引用统计	被引频次：1[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/20406
专题	第二临床医学院，附属第二医院、育英儿童医院检验医学院（生命科学学院、生物学实验教学中心）附属第二医院
通讯作者	Gao, Xiang
作者单位	1.The Affiliated Kangning Hospital of Wenzhou Medical University,The Second Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 2.State Key Laboratory of Freshwater Ecology and Biotechnology,Institute of Hydrobiology,Chinese Academy of Sciences,Wuhan,China; 3.School of Laboratory Medicine and Life Science,Wenzhou Medical University,Wenzhou,325000,China; 4.Department of Biostatistics,Epidemiology and Informatics,Perelman School of Medicine,University of Pennsylvania,Philadelphia,China; 5.Institute of Infectious Liver Disease,Tongji Hospital of Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China; 6.Institute of Psychiatry,Psychology and Neuroscience,King's College London,London,United Kingdom; 7.An-Nan Hospital,China Medical University,Tainan,Taiwan; 8.Central Laboratory,Scientific Research Department,Renmin Hospital of Wuhan University,Wuhan,China
第一作者单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院
通讯作者单位	其他_附属康宁医院（温州市康宁医院）
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院
推荐引用方式 GB/T 7714	Shi, Xulai,Guan, Kaiyu,Peng, Xuyan,et al. Ghrelin modulates dopaminergic neuron formation and attention deficit hyperactivity disorder-like behaviors: From animals to human models[J]. BRAIN BEHAVIOR AND IMMUNITY,2021,94:327-337.
APA	Shi, Xulai., Guan, Kaiyu., Peng, Xuyan., Xu, Bingru., Zhou, Xianyong., ... & Li, Xi. (2021). Ghrelin modulates dopaminergic neuron formation and attention deficit hyperactivity disorder-like behaviors: From animals to human models. BRAIN BEHAVIOR AND IMMUNITY, 94, 327-337.
MLA	Shi, Xulai,et al."Ghrelin modulates dopaminergic neuron formation and attention deficit hyperactivity disorder-like behaviors: From animals to human models".BRAIN BEHAVIOR AND IMMUNITY 94(2021):327-337.