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...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.展开更多
基金supported by the National Natural Science Foundation of China (32471049,32170984,32471188,32200802)Natural Science Foundation of Shandong Province (ZR2023QH110)。
文摘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.
