Genetic inactivation of the adenosine A2A receptor exacerbates brain damage in mice with experimental autoimmune encephalomyelitis

doi:10.1111/j.1471-4159.2012.07807.x

科研成果详情

题名	Genetic inactivation of the adenosine A2A receptor exacerbates brain damage in mice with experimental autoimmune encephalomyelitis
作者	Yao, Shu-Qin 1; Li, Zheng-Zheng1; Huang, Qing-Yuan 2; Li, Fang1; Wang, Zhao-Wei1; Augusto, Elisabete 2; He, Jin-Cai1; Wang, Xiao-Tong1; Chen, Jiang-Fan1,2; Zheng, Rong-Yuan1
发表日期	2012-10
发表期刊	JOURNAL OF NEUROCHEMISTRY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	adenosine A1 receptors adenosine A2A receptors CD4+T cells experimental autoimmune encephalomyelitis (EAE) microglial cells multiple sclerosis
其他关键词	CD8(+) T-CELLS ; CENTRAL-NERVOUS-SYSTEM ; EMERGING THERAPEUTIC TARGETS ; MULTIPLE-SCLEROSIS ; A(2A) RECEPTORS ; SPINAL-CORD ; FOCAL ISCHEMIA ; MOUSE STRIATUM ; TISSUE-DAMAGE ; ADULT RATS
摘要	Studies with multiple sclerosis patients and animal models of experimental autoimmune encephalomyelitis (EAE) implicate adenosine and adenosine receptors in modulation of neuroinflammation and brain injury. Although the involvement of the A1 receptor has been recently demonstrated, the role of the adenosine A2A receptor (A2AR) in development of EAE pathology is largely unknown. Using mice with genetic inactivation of the A2A receptor, we provide direct evidence that loss of the A2AR exacerbates EAE pathology in mice. Compared with wild-type mice, A2AR knockout mice injected with myelin oligodendroglia glycoprotein peptide had a higher incidence of EAE and exhibited higher neurological deficit scores and greater decrease in body weight. A2AR knockout mice displayed increased inflammatory cell infiltration and enhanced microglial cell activation in cortex, brainstem, and spinal cord. In addition, demyelination and axonal damage in brainstem were exacerbated, levels of Th1 cytokines increased, and Th2 cytokines decreased. Collectively, these findings suggest that extracellular adenosine acting at A2ARs triggers an important neuroprotective mechanism. Thus, the A2A receptor is a potential target for therapeutic approaches to multiple sclerosis.
资助项目	Wenzhou Medical College Key Research Project [30328015]; Joint Found of China Ministry of Public Health-Zhejiang Bureau of Health [WKJ 2005-2-041]; Wenzhou Science &Technology bureau [H20100014]; Building Funding of Zhejiang Key Subject (Pharmacology and Biochemical Pharmaceutics); US public health grant [(NIH) NS41083]; NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [R01NS041083] Funding Source: NIH RePORTER
出版者	WILEY-BLACKWELL
出版地	HOBOKEN
ISSN	0022-3042
EISSN	1471-4159
卷号	123 期号:1 页码:100-112
DOI	10.1111/j.1471-4159.2012.07807.x
页数	13
WOS类目	Biochemistry & Molecular Biology ; Neurosciences
WOS研究方向	Biochemistry & Molecular Biology ; Neurosciences & Neurology
WOS记录号	WOS:000308631800009
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	22639925
SCOPUSEID	2-s2.0-84866251649
通讯作者地址	[Chen, Jiang-Fan]Department of Neurology,Wenzhou Medical College,First Affiliated Hospital,China
Scopus学科分类	Biochemistry;Cellular and Molecular Neuroscience
引用统计	被引频次：55[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/16843
专题	第二临床医学院、附属第二医院、育英儿童医院_神经病学附属第一医院药学院（分析测试中心）_实验神经生物研究所
通讯作者	Chen, Jiang-Fan
作者单位	1.Department of Neurology,Wenzhou Medical College,First Affiliated Hospital,China; 2.Department of Neurology,Boston University,School of Medicine,715 Albany Street, C329,United States
第一作者单位	附属第一医院
通讯作者单位	附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Yao, Shu-Qin,Li, Zheng-Zheng,Huang, Qing-Yuan,et al. Genetic inactivation of the adenosine A2A receptor exacerbates brain damage in mice with experimental autoimmune encephalomyelitis[J]. JOURNAL OF NEUROCHEMISTRY,2012,123(1):100-112.
APA	Yao, Shu-Qin., Li, Zheng-Zheng., Huang, Qing-Yuan., Li, Fang., Wang, Zhao-Wei., ... & Zheng, Rong-Yuan. (2012). Genetic inactivation of the adenosine A2A receptor exacerbates brain damage in mice with experimental autoimmune encephalomyelitis. JOURNAL OF NEUROCHEMISTRY, 123(1), 100-112.
MLA	Yao, Shu-Qin,et al."Genetic inactivation of the adenosine A2A receptor exacerbates brain damage in mice with experimental autoimmune encephalomyelitis".JOURNAL OF NEUROCHEMISTRY 123.1(2012):100-112.