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一种稳定建立的小鼠两点注射溶血磷脂酰胆碱诱导的局灶性脱髓鞘模型。

A Stably Established Two-Point Injection of Lysophosphatidylcholine-Induced Focal Demyelination Model in Mice.

机构信息

Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.

Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology;

出版信息

J Vis Exp. 2022 May 11(183). doi: 10.3791/64059.

DOI:10.3791/64059
PMID:35635470
Abstract

Receptor-mediated lysophospholipid signaling contributes to the pathophysiology of diverse neurological diseases, especially multiple sclerosis (MS). Lysophosphatidylcholine (LPC) is an endogenous lysophospholipid associated with inflammation, and it could induce rapid damage with toxicity to myelin lipids, leading to focal demyelination. Here, a detailed protocol is presented for stereotactic two-point LPC injection that could directly cause severe demyelination and replicate the experimental demyelination injury quickly and stably in mice by surgical procedure. Thus, this model is highly relevant to demyelination diseases, especially MS, and it can contribute to the related advancing clinically-relevant research. Also, immunofluorescence and Luxol fast blue staining methods were used to depict the time course of demyelination in the corpus callosum of mice injected with LPC. In addition, the behavioral method was used to evaluate the cognitive function of mice after modeling. Overall, the two-point injection of lysophosphatidylcholine via a stereotaxic frame is a stable and reproducible method to generate a demyelination model in mice for further study.

摘要

受体介导的溶血磷脂信号通路参与多种神经疾病的病理生理学过程,特别是多发性硬化症(MS)。溶血磷脂酰胆碱(LPC)是一种与炎症相关的内源性溶血磷脂,它可诱导快速损伤,并对髓磷脂脂质产生毒性,导致局灶性脱髓鞘。这里,我们提供了一种详细的立体定向两点 LPC 注射方案,通过手术程序可以直接导致严重的脱髓鞘,并快速且稳定地在小鼠中复制实验性脱髓鞘损伤。因此,该模型与脱髓鞘疾病,特别是多发性硬化症高度相关,可促进相关的具有临床意义的研究。此外,我们还使用免疫荧光和卢索快速蓝染色方法描绘了 LPC 注射小鼠胼胝体脱髓鞘的时间过程。此外,我们还使用行为学方法评估了建模后小鼠的认知功能。总之,通过立体定向框架进行两点溶血磷脂酰胆碱注射是一种稳定且可重复的方法,可在小鼠中产生脱髓鞘模型,以进一步研究。

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引用本文的文献

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Front Mol Neurosci. 2022 Nov 3;15:995477. doi: 10.3389/fnmol.2022.995477. eCollection 2022.