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富氧环境暴露对小鼠大脑脂质组学的比较研究。

Comparative lipidomics of mouse brain exposed to enriched environment.

机构信息

Eisai Company, Limited, Ibaraki 300-2635, Japan; and.

出版信息

J Lipid Res. 2013 Oct;54(10):2687-96. doi: 10.1194/jlr.M038075. Epub 2013 Jul 6.

Abstract

Several studies have shown that housing conditions and environmental exposure to a series of stimuli lead to behavior improvement in several species. While more works have been focused on illustrating changes of the proteome and transcriptome following enriched environment exposure in mice, little has been done to understand changes in the brain metabolome in this paradigm due to the complexity of this type of analysis. In this paper, lipidomics focused on phospholipids and gangliosides were conducted for brain tissues of mice exposed to enriched or impoverished conditions. We optimized previously reported method and established a reliable relative comparison method for phospholipids and gangliosides in brain tissue using prefractionation with weak anion exchange cartridge. We used liquid chromatography mass spectrometry to explore metabolic signatures of the cerebral cortex and hippocampus after confirming the animals had significant memory differences using the fear conditioning paradigm and brain immunohistochemistry. Although both cerebral cortex and hippocampus regions did not show major alterations in ganglioside composition, we found significant differences in a series of phospholipids containing 22:6 fatty acid in the prefrontal cortex, indicating that environmental enrichment and impoverished housing conditions might be a relevant paradigm to study aberrant lipid metabolism of docosahexaenoic acid consumption. Our study highlights the hypothesis-generating potential of lipidomics and identifies novel region-specific lipid changes possibly linked not only to change of memory function in these models, but also to help us better understand how lipid changes may contribute to memory disorders.

摘要

多项研究表明,住房条件和环境暴露于一系列刺激因素会导致多种物种的行为改善。虽然更多的工作集中在阐明丰富环境暴露后小鼠的蛋白质组和转录组的变化,但由于这种类型的分析很复杂,对于理解该范式下大脑代谢组的变化知之甚少。在本文中,对暴露于丰富或贫瘠环境的小鼠脑组织进行了脂质组学研究,重点是磷脂和神经节苷脂。我们优化了先前报道的方法,并使用弱阴离子交换柱进行预分级,建立了一种可靠的脑组织中磷脂和神经节苷脂相对比较方法。我们使用液相色谱质谱法来探索大脑皮层和海马体的代谢特征,在使用恐惧条件反射范式确认动物有明显的记忆差异后,并对大脑进行免疫组织化学分析。尽管大脑皮层和海马体区域的神经节苷脂组成没有发生重大变化,但我们在前额皮质中发现了一系列含有 22:6 脂肪酸的磷脂存在显著差异,这表明环境丰富和贫瘠的住房条件可能是研究二十二碳六烯酸消耗异常脂质代谢的相关范式。我们的研究强调了脂质组学的产生假说的潜力,并确定了可能不仅与这些模型中记忆功能变化有关的新型区域特异性脂质变化,还有助于我们更好地理解脂质变化如何有助于记忆障碍。

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