Comparative Analysis of Lipid Extracts and Imaging Mass Spectrometry for Evaluating Cerebral White Matter Biochemical Pathology in an Experimental Second-Hand Cigarette Smoke Exposure Model

Abstract

Background White matter injury and degeneration are common features of developmental and aging-associated diseases, yet their pathobiological bases are poorly understood. However, recent advances in Matrix-Assisted Laser Desorption Ionization (MALDI) instruments and chemistry have provided critical tools for myelin-lipid analytical research. Design This study characterizes Cigarette Smoke (CS) exposure effects on frontal lobe lipid ion profiles in adult male A/J mice that had been exposed to air for 8 weeks (A8), CS for 4 (CS4) or 8 weeks (CS8), or CS8 followed by 2 weeks recovery (CS8+R). MALDI data acquired by analysis of lipid extracts plated onto a ground steel target (high through-put) were compared with Imaging Mass Spectrometry (IMS). Results MALDI-time-of-flight (TOF) detected 120 lipid ions with m/z's of 600 to 1300 (phospholipids and sulfatides) in samples plated onto the steel target or analyzed by IMS, but just 25 ions (18%) were detected by both methods. IMS more effectively detected ions in the highest m/z range, whereas the extracts had abundant middle-range m/z ions. The experimental groups were better discriminated by PCA and R-generated heat map hierarchical clustering of IMS data than lipid extract data. On the other hand, both methods clearly delineated the CS4, CS8 and CS8+R experimental groups from control. Conclusions MALDI analysis of brain lipid extracts plated onto a ground steel target for high through-put studies, or imaged directly in tissue can be used to assess biochemical pathology of white matter neurodegeneration and responses to treatment.