Xizhen Ma, Guorui Jia, Mengyu Li, Shenghan Zhang, Zhaoxin Wang, Ning Song, Yingjuan Liu, Junxia Xie. 2024. Elevated CXCL1 triggers dopaminergic neuron loss in the substantia nigra of C57BL/6J mice: evaluation of a novel Parkinsonian mouse model. Zoological Research. DOI: 10.24272/j.issn.2095-8137.2024.228
Citation: Xizhen Ma, Guorui Jia, Mengyu Li, Shenghan Zhang, Zhaoxin Wang, Ning Song, Yingjuan Liu, Junxia Xie. 2024. Elevated CXCL1 triggers dopaminergic neuron loss in the substantia nigra of C57BL/6J mice: evaluation of a novel Parkinsonian mouse model. Zoological Research. DOI: 10.24272/j.issn.2095-8137.2024.228

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

  • Substantial evidence points to the early onset of inflammation in the periphery during the development of Parkinson's disease (PD), lending credence to the "body-first" hypothesis. However, there remains a notable absence of PD animal models that are specifically induced by inflammatory cytokines. Here we present a novel mouse model mediated by the proinflammatory cytokine, CXCL1, which identified in our previous study. We demonstrated the universality of CXCL1 in the PD models using the classic subacute and chronic MPTP mouse models. On these basis, 2-month-old C57BL/6J mice were intravenously injected with CXCL1 for two weeks (5 days per week) at a dose of 20 ng/kg/day. The motor disorders and pathological changes in the SN in the chronic MPTP model were successfully reproduced in these mice with CXCL1 intravenous injection, indicated that it could be a novel PD mouse model. The model highlights the involvement of the PPAR signaling pathway in inflammation-mediated neuronal damage by CXCL1. Linoleic acid, a PPAR-γ activator, counteracted both MPTP and CXCL1-induced toxicity and reduced serum CXCL1 levels. In addition, the CXCL1-injected mouse model reduces the cycle-time of chronic PD mouse model to two weeks, offers a promising tool for studying the inflammatory processes in PD, providing insights into potential therapeutic targets.
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