Tong Ming, Leão Raiane, Vimbela Gina V, Yalcin Emine B, Kay Jared, Krotow Alexander, de la Monte Suzanne M
Liver Research Center, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, United States; Division of Gastroenterology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, United States; Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, United States.
Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Mol Cell Neurosci. 2017 Jul;82:23-34. doi: 10.1016/j.mcn.2017.04.010. Epub 2017 Apr 21.
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.
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).
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).
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.
白质是阿尔茨海默病（AD）早期且重要但未得到充分评估的靶点。胰岛素和胰岛素样生长因子抵抗导致的代谢损伤会促使白质退化，因为相应的信号转导通路维持着少突胶质细胞的功能和存活。
本研究使用了散发性AD模型，成年Long Evans大鼠通过脑室内注射链脲佐菌素（i.c. STZ）引发AD型神经退行性变。通过基质辅助激光解吸/电离成像质谱（MALDI-IMS）对颞叶白质脂质离子谱进行表征。
虽然i.c. STZ组和对照组中表达的脂质离子种类基本相同，但i.c. STZ主要改变了各种脂质离子的丰度。相应地，通过主成分分析和数据条图可将i.c. STZ组与对照组区分开来。i.c. STZ主要降低了低质荷比（小于810）脂质离子以及较高质荷比范围脂质（质荷比964 - 986）的表达，并增加了质荷比在888至937之间的脂质离子的表达。磷脂主要包含在受i.c. STZ抑制的簇中，而硫脂和磷脂均因i.c. STZ而增加。然而，卡方分析表明i.c. STZ显著诱导了磷脂的趋势性降低和硫脂的增加（P<0.00001）。
散发性AD的i.c. STZ模型与颞叶白质脂质广泛且持续的异常有关。这些发现表明，i.c. STZ模型可用于临床前研究，以评估治疗措施恢复AD中白质完整性的能力。
