Optimized integration of metabolomics and lipidomics reveals brain region-specific changes of oxidative stress and neuroinflammation in type 1 diabetic mice with cognitive decline.
Optimized integration of metabolomics and lipidomics reveals brain region-specific changes of oxidative stress and neuroinflammation in type 1 diabetic mice with cognitive decline.
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DOI：
10.1016/j.jare.2022.02.011
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发表时间：
2023-01
影响因子：
10.7
通讯作者：
Zheng, Hong
中科院分区：
文献类型：
--
作者：
Xiong, Fen;Gong, Kaiyan;Xu, Hangying;Tu, Yingxin;Lu, Jiahui;Zhou, Yiyang;He, Wenting;Li, Wenqing;Li, Chen;Zhao, Liangcai;Gao, Hongchang;Zheng, Hong
使用优化的提取方法在小鼠大脑中检测到超过 4000 种代谢物和 6000 种脂质特征。在 T1D 小鼠中，额叶皮层的脂质紊乱比海马更显着。在 T1D 小鼠中，额叶皮层的神经炎症比海马更明显。大脑区域特定的氧化应激变化可能会导致糖尿病认知能力下降。额叶皮层可能是 T1D 小鼠氧化应激的主要目标大脑区域。 1 型糖尿病 (T1D) 会导致认知能力下降，并与大脑代谢紊乱有关，但其潜在的分子机制仍不清楚。本研究的目的是利用代谢组学和脂质组学探讨 T1D 引起的认知障碍的分子机制。我们开发了一种基于 UPLC-Q-TOF-MS 的脑组织代谢组学和脂质组学的优化整合方法，并分析了认知衰退的 T1D 雄性小鼠 (T1DCD) 和年龄匹配对照 (CONT) 小鼠海马和额叶皮层代谢物和脂质谱的综合特征。结果表明，T1DCD小鼠相对于CONT小鼠存在区域特异性的脑代谢紊乱，并且T1DCD小鼠的额叶皮层表现出比海马更高的脂质过氧化。基于代谢变化，我们发现小胶质细胞在糖尿病条件下被激活，从而促进氧化应激和神经炎症，导致神经元损伤，并且该事件在额叶皮质中比海马体中更为明显。我们的研究结果表明，氧化应激和神经炎症的大脑区域特异性变化可能会导致糖尿病认知能力下降，而额叶皮层可能是比海马体更脆弱的大脑区域。
Over 4000 metabolite and 6000 lipid features were detected in the mouse brain using the optimized extraction method. Lipid disorders are more significant in the frontal cortex than the hippocampus in T1D mice. Neuroinflammation is more pronounced in the frontal cortex than the hippocampus in T1D mice. Brain region-specific shifts in oxidant stress may cause diabetic cognitive decline. The frontal cortex might be a major target brain region of oxidant stress in T1D mice. Type 1 diabetes (T1D) causes cognitive decline and has been associated with brain metabolic disorders, but its potential molecular mechanisms remain unclear. The purpose of this study was to explore the molecular mechanisms underlying T1D-induced cognitive impairment using metabolomics and lipidomics. We developed an optimized integration approach of metabolomics and lipidomics for brain tissue based on UPLC-Q-TOF-MS and analyzed a comprehensive characterization of metabolite and lipid profiles in the hippocampus and frontal cortex of T1D male mice with cognitive decline (T1DCD) and age-matched control (CONT) mice. The results show that T1DCD mice had brain metabolic disorders in a region-specific manner relative to CONT mice, and the frontal cortex exhibited a higher lipid peroxidation than the hippocampus in T1DCD mice. Based on metabolic changes, we found that microglia was activated under diabetic condition and thereby promoted oxidative stress and neuroinflammation, leading to neuronal injury, and this event was more pronounced in the frontal cortex than the hippocampus. Our results suggest that brain region-specific shifts in oxidative stress and neuroinflammation may contribute to diabetic cognitive decline, and the frontal cortex could be the more vulnerable brain region than the hippocampus.
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影响因子：
4
作者：
Elahi, Montasir;Hasan, Zafrul;Hattori, Nobutaka
通讯作者：
Hattori, Nobutaka
DOI：
10.1016/j.bbrc.2016.10.086
发表时间：
2017-01-15
影响因子：
3.1
作者：
Gaschler MM;Stockwell BR
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Stockwell BR
影响因子：
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Boylan JA;Lawrence KA;Downey JS;Gherardini FC
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DOI：
10.1038/s41574-018-0048-7
发表时间：
2018-10
期刊：
Nature reviews. Endocrinology
影响因子：
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作者：
Biessels GJ;Despa F
通讯作者：
Despa F
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影响因子：
48
作者：
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