MALDI mass spectrometry imaging discloses the decline of sulfoglycosphingolipid and glycerophosphoinositol species in the brain regions related to cognition in a mouse model of Alzheimer's disease
MALDI mass spectrometry imaging discloses the decline of sulfoglycosphingolipid and glycerophosphoinositol species in the brain regions related to cognition in a mouse model of Alzheimer's disease
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DOI：
10.1016/j.talanta.2023.125022
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发表时间：
2023-08-23
期刊：
影响因子：
6.1
通讯作者：
Wang，Chun-Yan
中科院分区：
文献类型：
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作者：
Zhang，Qi;Li，Yan;Wang，Chun-Yan
衰老和神经退行性疾病都伴随着大脑中的脂质扰动。了解脂质含量和功能活性的变化仍然是一个挑战，不仅因为脂质在许多领域发挥生物活性，而且还因为鉴定脂质及其代谢物的技术限制。在本研究中，我们旨在通过使用质谱成像（MSI）来评估脑脂质在阿尔茨海默病（AD）样病理学中如何改变。通过基质辅助激光解吸电离 (MALDI) MSI 测定，比较 APP/PS1 小鼠和年龄匹配的野生型 (WT) 小鼠大脑中脂质的空间分布和相对丰度。将比较与使用分光光度法的分析相关联，以确定不同脑区域脑硫苷脂的相对含量。确定了 APP/PS1 和 WT 小鼠脑脂质的显着变化：八种磺基鞘糖脂种类，即硫苷脂/硫酸化己糖基神经酰胺 (ShexCer) 和两种甘油磷酸肌醇 (GroPIn) 种类，PI 36:4 和 PI 38:4。 APP/PS1 小鼠大脑中这些 ShexCer 和 GroPIn 物种空间分布的下降与学习和记忆相关的大脑区域有关。与年轻的 WT 小鼠相比，老年 WT 小鼠的 ShexCer 和 GroPIn 物种水平显着降低。我们的结果为评估脑脂质代谢对衰老和神经退行性大脑的影响提供了技术线索。脑硫苷脂和 GroPINs 的减少可能是大脑衰老和 AD 病理过程中的关键标志物。适当的脂质补充可能是 AD 治疗策略的重要潜力。
Aging and neurodegenerative disease are accompanied by lipid perturbations in the brain. Understanding the changes in the contents and functional activity of lipids remains a challenge not only because of the many areas in which lipids perform bioactivities but also because of the technical limitations in identifying lipids and their metabolites. In the present study, we aimed to evaluate how brain lipids are altered in Alzheimer's disease (AD)-like pathology by using mass spectrometry imaging (MSI). The spatial distributions and relative abundances of lipids in the brains were compared between APP/PS1 mice and their age-matched wild-type (WT) mice by matrix-assisted laser desorption ionization (MALDI) MSI assays. The comparisons were correlated with the analysis using a spectrophotometric method to determine the relative contents of sulfatides in different brain regions. Significant changes of brain lipids between APP/PS1 and WT mice were identified: eight sulfoglycosphingolipid species, namely, sulfatides/sulfated hexosyl ceramides (ShexCer) and two glycerophosphoinositol (GroPIn) species, PI 36:4 and PI 38:4. The declines in the spatial distributions of these ShexCer and GroPIn species in the APP/PS1 mice brains were associated with learning- and memory-related brain regions. Compared with young WT mice, aged WT mice showed significant decreases in the levels of these ShexCer and GroPIn species. Our results provide technical clues for assessing the impact of brain lipid metabolism on the senescent and neurodegenerative brain. The decline in sulfatides and GroPIns may be crucial markers during brain senescence and AD pathology. Appropriate lipid complementation might be important potentials as a therapeutic strategy for AD.