BACKGROUND White matter is an early and important yet under-evaluated target of Alzheimer's disease (AD). Metabolic impairments due to insulin and insulin-like growth factor resistance contribute to white matter degeneration because corresponding signal transduction pathways maintain oligodendrocyte function and survival. METHODS This study utilized a model of sporadic AD in which adult Long Evans rats administered intracerebral streptozotocin (i.c. STZ) developed AD-type neurodegeneration. Temporal lobe white matter lipid ion profiles were characterized by matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). RESULTS Although the lipid ion species expressed in the i.c. STZ and control groups were virtually identical, i.c. STZ mainly altered the abundances of various lipid ions. Correspondingly, the i.c. STZ group was distinguished from control by principal component analysis and data bar plots. i.c. STZ mainly reduced expression of lipid ions with low m/z's (less than 810) as well as the upper range m/z lipids (m/z 964-986), and increased expression of lipid ions with m/z's between 888 and 937. Phospholipids were mainly included among the clusters inhibited by i.c. STZ, while both sulfatides and phospholipids were increased by i.c. STZ. However, Chi-Square analysis demonstrated significant i.c. STZ-induced trend reductions in phospholipids and increases in sulfatides (P<0.00001). CONCLUSIONS The i.c. STZ model of sporadic AD is associated with broad and sustained abnormalities in temporal lobe white matter lipids. The findings suggest that the i.c. STZ model could be used for pre-clinical studies to assess therapeutic measures for their ability to restore white matter integrity in AD.

中文翻译：

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在偶发性阿尔茨海默氏病实验模型中，颞叶白质脂质离子谱发生改变。

背景技术白质是阿尔茨海默氏病（AD）的早期且重要但仍被低估的靶标。由于相应的信号转导途径维持少突胶质细胞功能和存活，因此由于胰岛素和类胰岛素生长因子抗性引起的代谢损伤会导致白质变性。方法该研究利用了散发性AD模型，其中成年的Long Evans大鼠使用了脑内链脲佐菌素（ic STZ），发展为AD型神经变性。通过基质辅助激光解吸/电离成像质谱（MALDI-IMS）表征颞叶白质脂质离子分布。结果尽管ic STZ和对照组中表达的脂质离子种类几乎相同，但ic STZ主要改变了各种脂质离子的丰度。相应地，ic STZ组通过主成分分析和数据条形图与对照区分开。ic STZ主要降低m / z较低（小于810）的脂质离子的表达以及m / z较高范围的脂质（m / z 964-986），而m / z介于888和211之间的脂质离子表达增加。 937.磷脂主要包括在ic STZ抑制的簇中，而硫化物和磷脂均受ic STZ抑制。但是，卡方分析显示ic STZ诱导的磷脂趋势显着减少，而硫苷脂则增加（P <0.00001）。结论散发性AD的ic STZ模型与颞叶白质脂质广泛而持续的异常有关。研究结果表明