Cigarette Smoke-Induced Alterations in Frontal White Matter Lipid Profiles Demonstrated by MALDI-Imaging Mass Spectrometry: Relevance to Alzheimer’s Disease

Autor: Suzanne M. de la Monte, Ming Tong, Alexander Krotow, Jared Kay, Amit R Agarwal, Enrique Cadenas, Kavin M Nunez
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Enzyme-Linked Immunosorbent Assay
Dinoprost
Protein oxidation
medicine.disease_cause
Article
Protein Carbonylation
White matter
Lipid peroxidation
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
Animals
Phospholipids
Phosphatidylethanolamine
Aldehydes
Analysis of Variance
Principal Component Analysis
medicine.diagnostic_test
General Neuroscience
Smoking
General Medicine
Phosphatidylserine
Lipid Metabolism
White Matter
Sphingolipid
Frontal Lobe
Substance Withdrawal Syndrome
Disease Models
Animal
Psychiatry and Mental health
Clinical Psychology
030104 developmental biology
medicine.anatomical_structure
Endocrinology
chemistry
Biochemistry
Spectrometry
Mass
Matrix-Assisted Laser Desorption-Ionization
lipids (amino acids
peptides
and proteins)
Geriatrics and Gerontology
Lipid profile
030217 neurology & neurosurgery
Oxidative stress
Zdroj: Journal of Alzheimer's Disease. 51:151-163
ISSN: 1875-8908
1387-2877
DOI: 10.3233/jad-150916
Popis: BACKGROUND 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. OBJECTIVE 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). METHODS 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. RESULTS 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. CONCLUSION 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.
Databáze: OpenAIRE
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