Elevated CXCL1 triggers dopaminergic neuronal loss in the substantia nigra of C57BL/6J mice: Evaluation of a novel Parkinsonian mouse model
Year: 2024
Type: article
Abstract: 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-γ activator, significantly mitigated MPTP- and CXCL1-induced toxicity and reduced serum CXCL1 levels. 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.
Source: 动物学研究
Authors: Ma Xi-Zhen, 青岛大学脑科学与疾病研究院基础医学院山东省神经系统疾病发病与预防重点实验室, 山东 青岛 266071, 中国, Jia Guo-Rui, Li Meng-Yu, Zhang Sheng-Han, Wang Zhao-Xin, Song Ning, Liu Ying-Juan, Xie Jun-Xia, 康复大学生命科学与健康学院, 山东 青岛 266113, 中国
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4404623898