Fibroblast Growth Factor 21 Modulates Microglial Polarization That Attenuates Neurodegeneration in Mice and Cellular Models of Parkinson's Disease

doi:10.3389/fnagi.2021.778527

科研成果详情

题名	Fibroblast Growth Factor 21 Modulates Microglial Polarization That Attenuates Neurodegeneration in Mice and Cellular Models of Parkinson's Disease
作者	Yang, Changwei 1,2; Wang, Wuqiong 1; Deng, Pengxi 1; Li, Chen 1; Zhao, Liangcai1; Gao, Hongchang1
发表日期	2021-12-22
发表期刊	FRONTIERS IN AGING NEUROSCIENCE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	dopaminergic neurodegeneration fibroblast growth factor microglia phenotype neuroinflammation sirtuin 1 cognitive decline
其他关键词	DOPAMINERGIC NEURODEGENERATION ; BRAIN ; ALPHA ; FGF21 ; NEUROPROTECTION ; PHENOTYPE ; CELLS
摘要	Microglial polarization and the subsequent neuroinflammatory response were identified as key contributors to the progress of Parkinson's disease (PD). Researchers have shown that fibroblast growth factor 21 (FGF21) plays multiple biological functions, including anti-inflammation and neuroprotection. However, the knowledge of FGF21 on microglial polarization in PD in vivo is far from completion. In this study, both in vivo and in vitro models were used to investigate whether FGF21 enhances the brain function by modulating microglial polarization in PD. The protective effects of FGF21 in vivo were conducted using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mice model alongside intraperitoneally received FGF21. A behavioral test battery and tyrosine hydroxylase (TH) immunohistochemistry were conducted to evaluate the neuronal function and nigrostriatal tract integrity. Immunofluorescence assay and Western blot were used to examine M1/M2 microglial polarization. Then, a microglia-neuron co-culture system was adopted in vitro to identify the underlying molecular mechanisms of FGF21. The results showed that FGF21 significantly alleviated motor and cognitive impairment in mice with PD. FGF21 also protected TH-positive neuron cells in the striatum and midbrain. Mechanistically, FGF21 suppressed M1 microglial polarization and the subsequent mRNA expression of pro-inflammatory factors while promoting M2 microglial polarization with increasing anti-inflammatory factors in mice with PD. Furthermore, sirtuin 1 (SIRT1) and the nuclear factor-kappa B (NF-kappa B) pathway were involved in the FGF21-induced M2 microglial polarization. Conversely, SIRT1 inhibitor EX527 significantly prevented both the FGF21-induced SIRT1 expression and M2 microglial polarization. Moreover, FGF21 pretreatment of microglia significantly prevented neuronal cell apoptosis in a microglia-neuron co-culture system. In conclusion, our data demonstrate that FGF21 exerted its protective effects in the pathology of PD through SIRT1/NF-kappa B pathway-mediated microglial polarization. Given the safety record of human clinical trials, FGF21 could be a promising therapy for clinical trials to ameliorate motor and nonmotor deficits in patients with PD.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21974096, 81771386]; Natural Science Foundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang Province [LQ19H070001]
出版者	FRONTIERS MEDIA SA
出版地	LAUSANNE
ISSN	1663-4365
卷号	13 页码:778527
DOI	10.3389/fnagi.2021.778527
页数	15
WOS类目	Geriatrics & Gerontology ; Neurosciences
WOS研究方向	Geriatrics & Gerontology ; Neurosciences & Neurology
WOS记录号	WOS:000743713500001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	35002679
PMC记录号	PMC8727910
SCOPUSEID	2-s2.0-85122283369
通讯作者地址	[Gao, Hongchang]School of Pharmaceutical Science,Institute of Metabonomics Medical NMR,Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Aging;Cognitive Neuroscience
引用统计	被引频次：3[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/3935
专题	附属第二医院_核磁共振室
通讯作者	Gao, Hongchang
作者单位	1.School of Pharmaceutical Science,Institute of Metabonomics Medical NMR,Wenzhou Medical University,Wenzhou,China; 2.School of Public Health,Fujian Medical University,Fuzhou,China
第一作者单位	温州医科大学
通讯作者单位	温州医科大学
第一作者的第一单位	温州医科大学
推荐引用方式 GB/T 7714	Yang, Changwei,Wang, Wuqiong,Deng, Pengxi,et al. Fibroblast Growth Factor 21 Modulates Microglial Polarization That Attenuates Neurodegeneration in Mice and Cellular Models of Parkinson's Disease[J]. FRONTIERS IN AGING NEUROSCIENCE,2021,13:778527.
APA	Yang, Changwei, Wang, Wuqiong, Deng, Pengxi, Li, Chen, Zhao, Liangcai, & Gao, Hongchang. (2021). Fibroblast Growth Factor 21 Modulates Microglial Polarization That Attenuates Neurodegeneration in Mice and Cellular Models of Parkinson's Disease. FRONTIERS IN AGING NEUROSCIENCE, 13, 778527.
MLA	Yang, Changwei,et al."Fibroblast Growth Factor 21 Modulates Microglial Polarization That Attenuates Neurodegeneration in Mice and Cellular Models of Parkinson's Disease".FRONTIERS IN AGING NEUROSCIENCE 13(2021):778527.