Nunez Kavin, Kay Jared, Krotow Alexander, Tong Ming, Agarwal Amit R, Cadenas Enrique, de la Monte Suzanne M
Liver Research Center, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Providence, RI, USA.
Molecular Pharmacology, Physiology, and Biotechnology, Providence, RI, USA.
J Alzheimers Dis. 2016;51(1):151-63. doi: 10.3233/JAD-150916.
Meta-analysis has shown that smokers have significantly increased risks for Alzheimer's disease (AD), and neuroimaging studies showed that smoking alters white matter (WM) structural integrity.
Herein, we characterize the effects of cigarette smoke (CS) exposures and withdrawal on WM myelin lipid composition using matrix assisted laser desorption and ionization-imaging mass spectrometry (MALDI-IMS).
Young adult male A/J mice were exposed to air (8 weeks; A8), CS (4 or 8 weeks; CS4, CS8), or CS8 followed by 2 weeks recovery (CS8 + R). Frontal lobe WM was examined for indices of lipid and protein oxidation and lipid profile alterations by MALDI-IMS. Lipid ions were identified by MS/MS with the LIPID MAPS prediction tools database. Inter-group comparisons were made using principal component analysis and R-generated heatmap.
CS increased lipid and protein adducts such that higher levels were present in CS8 compared with CS4 samples. CS8 + R reversed CS8 effects and normalized the levels of oxidative stress. MALDI-IMS demonstrated striking CS-associated alterations in WM lipid profiles characterized by either reductions or increases in phospholipids (phosphatidylinositol, phosphatidylserine, phosphatidylcholine, or phosphatidylethanolamine) and sphingolipids (sulfatides), and partial reversal of CS's inhibitory effects with recovery. The heatmap hierarchical dendrogram and PCA distinguished CS exposure, duration, and withdrawal effects on WM lipid profiles.
CS-mediated WM degeneration is associated with lipid peroxidation, protein oxidative injury, and alterations in myelin lipid composition, including shifts in phospholipids and sphingolipids needed for membrane integrity, plasticity, and intracellular signaling. Future goals are to delineate WM abnormalities in AD using MALDI-IMS, and couple the findings with MRI-mass spectroscopy to improve in vivo diagnostics and early detection of brain biochemical responses to treatment.
荟萃分析表明，吸烟者患阿尔茨海默病（AD）的风险显著增加，神经影像学研究表明，吸烟会改变白质（WM）的结构完整性。
在此，我们使用基质辅助激光解吸电离成像质谱（MALDI-IMS）来描述香烟烟雾（CS）暴露和戒断对WM髓磷脂脂质组成的影响。
将年轻成年雄性A/J小鼠暴露于空气（8周；A8）、CS（4或8周；CS4、CS8）或CS8后恢复2周（CS8+R）。通过MALDI-IMS检查额叶WM的脂质和蛋白质氧化指标以及脂质谱变化。使用MS/MS和脂质地图预测工具数据库鉴定脂质离子。使用主成分分析和R生成的热图进行组间比较。
CS增加了脂质和蛋白质加合物，使得CS8样本中的水平高于CS4样本。CS8+R逆转了CS8的影响并使氧化应激水平正常化。MALDI-IMS显示WM脂质谱中与CS相关的显著变化，其特征是磷脂（磷脂酰肌醇、磷脂酰丝氨酸、磷脂酰胆碱或磷脂酰乙醇胺）和鞘脂（硫脂）减少或增加，并且随着恢复，CS的抑制作用部分逆转。热图层次树状图和主成分分析区分了CS暴露、持续时间和戒断对WM脂质谱的影响。
CS介导的WM变性与脂质过氧化、蛋白质氧化损伤以及髓磷脂脂质组成的改变有关，包括膜完整性、可塑性和细胞内信号传导所需的磷脂和鞘脂的变化。未来的目标是使用MALDI-IMS描绘AD中的WM异常，并将这些发现与MRI-质谱相结合以改善体内诊断和脑生化反应治疗的早期检测。
