Elevated CXCL1 triggers dopaminergic neuronal loss in the substantia nigra of C57BL/6J mice:Evaluation of a novel Parkinsonian mouse model  

作　　者：Xi-Zhen Ma Guo-Rui Jia Meng-Yu Li Sheng-Han Zhang Zhao-Xin Wang Ning Song Ying-Juan Liu Jun-Xia Xie 

机构地区：[1]Institute of Brain Science and Disease,School of Basic Medicine,Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders,Qingdao University,Qingdao,Shandong 266071,China [2]College of Life Sciences and Health,University of Health and Rehabilitation Science,Qingdao,Shandong 266113,China

出　　处：《Zoological Research》2025年第1期225-235,共11页动物学研究(英文)

基　　金：supported by the National Natural Science Foundation of China (32471049,32170984,32471188,32200802);Natural Science Foundation of Shandong Province (ZR2023QH110)。

摘　　要：Substantial evidence points to the early onset of peripheral inflammation in the development of Parkinson's disease(PD),supporting the“body-first”hypothesis.However,there remains a notable absence of PD-specific animal models induced by inflammatory cytokines.This study introduces a novel mouse model of PD driven by the proinflammatory cytokine CXCL1,identified in our previous research.The involvement of CXCL1 in PD pathogenesis was validated using subacute and chronic MPTP-induced mouse models.Based on these findings,2-month-old C57BL/6J mice were intravenously administered CXCL1(20 ng/kg/day)for 2 weeks(5 days per week),successfully replicating motor deficits and pathological alterations in the substantia nigra observed in the chronic MPTP model.These results demonstrate the potential of CXCL1-induced inflammation as a mechanism for PD modeling.The model revealed activation of the PPAR signaling pathway in CXCL1-mediated neuronal damage by CXCL1.Linoleic acid,a PPAR-γactivator,significantly mitigated MPTPand CXCL1-induced toxicity and reduced serum CXCL1levels.In addition,the CXCL1-injected mouse model shortened the timeline for developing chronic PD mouse model to 2 weeks,offering an efficient platform for studying inflammation-driven processes in PD.The findings provide critical insights into the inflammatory mechanisms underlying PD and identify promising therapeutic targets for intervention.

关 键 词：Parkinson’s disease Mouse model CXCL1 Inflammation PPAR signaling pathway 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]