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GM3 神经节苷脂与转 Tau 病模型大鼠神经原纤维缠结病理相关。

GM3 Ganglioside Linked to Neurofibrillary Pathology in a Transgenic Rat Model for Tauopathy.

机构信息

Institute of Neuroimmunology, Slovak Academy of Sciences, Dúbravská cesta 9, 84510 Bratislava, Slovakia.

Laboratory of Biomedical Microbiology and Immunology, University of Veterinary Medicine and Pharmacy, 04181 Kosice, Slovakia.

出版信息

Int J Mol Sci. 2021 Nov 22;22(22):12581. doi: 10.3390/ijms222212581.

DOI:10.3390/ijms222212581
PMID:34830461
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8622195/
Abstract

Glycosphingolipids (GSLs) are amphipathic lipids composed of a sphingoid base and a fatty acyl attached to a saccharide moiety. GSLs play an important role in signal transduction, directing proteins within the membrane, cell recognition, and modulation of cell adhesion. Gangliosides and sulfatides belong to a group of acidic GSLs, and numerous studies report their involvement in neurodevelopment, aging, and neurodegeneration. In this study, we used an approach based on hydrophilic interaction liquid chromatography (HILIC) coupled to high-resolution tandem mass spectrometry (HRMS/MS) to characterize the glycosphingolipid profile in rat brain tissue. Then, we screened characterized lipids aiming to identify changes in glycosphingolipid profiles in the normal aging process and tau pathology. Thorough screening of acidic glycosphingolipids in rat brain tissue revealed 117 ganglioside and 36 sulfatide species. Moreover, we found two ganglioside subclasses that were not previously characterized-GT1b-Ac2 and GQ1b-Ac2. The semi-targeted screening revealed significant changes in the levels of sulfatides and GM1a gangliosides during the aging process. In the transgenic SHR24 rat model for tauopathies, we found elevated levels of GM3 gangliosides which may indicate a higher rate of apoptotic processes.

摘要

糖鞘脂（GSLs）是由神经酰胺碱基和连接在糖部分上的脂肪酸组成的两亲性脂质。GSLs 在信号转导、膜内蛋白导向、细胞识别和细胞黏附调节中发挥重要作用。神经节苷脂和硫酸脑苷脂属于一组酸性 GSLs，许多研究报告称它们参与神经发育、衰老和神经退行性变。在这项研究中，我们使用了基于亲水相互作用液相色谱（HILIC）与高分辨率串联质谱（HRMS/MS）相结合的方法来描述大鼠脑组织中的糖鞘脂谱。然后，我们对特征性脂质进行了筛选，旨在确定在正常衰老过程中和 tau 病理中糖鞘脂谱的变化。对大鼠脑组织中酸性糖鞘脂的全面筛选揭示了 117 种神经节苷脂和 36 种硫酸脑苷脂。此外，我们发现了两种以前未表征的神经节苷脂亚类-GT1b-Ac2 和 GQ1b-Ac2。半靶向筛选显示在衰老过程中硫酸脑苷脂和 GM1a 神经节苷脂的水平发生了显著变化。在 tau 病的 SHR24 转基因大鼠模型中，我们发现 GM3 神经节苷脂水平升高，这可能表明凋亡过程的速度更高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96c2/8622195/cefacb9743fa/ijms-22-12581-g006.jpg
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