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Global changes of phospholipids identified by MALDI imaging mass spectrometry in a mouse model of Alzheimer's disease.

ABSTRACT: Alzheimer's disease (AD) is the most common form of dementia; however, at the present time there is no disease-modifying drug for AD. There is increasing evidence supporting the role of lipid changes in the process of normal cognitive aging and in the etiology of age-related neurodegenerative diseases. AD is characterized by the presence of intraneuronal protein clusters and extracellular aggregates of ?-amyloid (A?). Disrupted A? kinetics may activate intracellular signaling pathways, including tau hyperphosphorylation and proinflammatory pathways. We analyzed and visualized the lipid profiles of mouse brains using MALDI-TOF MS. Direct tissue analysis by MALDI-TOF imaging MS (IMS) can determine the relative abundance and spatial distribution of specific lipids in different tissues. We used 5XFAD mice that almost exclusively generate and rapidly accumulate massive cerebral levels of A?-42 (1). Our data showed changes in lipid distribution in the mouse frontal cortex, hippocampus, and subiculum, where A? plaques are first generated in AD. Our results suggest that MALDI-IMS is a powerful tool for analyzing the distribution of various phospholipids and that this application might provide novel insight into the prediction of disease.

SUBMITTER: Hong JH

PROVIDER: S-EPMC4689334 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Global changes of phospholipids identified by MALDI imaging mass spectrometry in a mouse model of Alzheimer's disease.

Hong Ji Hye JH Kang Jeong Won JW Kim Dong Kyu DK Baik Sung Hoon SH Kim Kyung Ho KH Shanta Selina Rahman SR Jung Jae Hun JH Mook-Jung Inhee I Kim Kwang Pyo KP

Journal of lipid research 20151104 1

Alzheimer's disease (AD) is the most common form of dementia; however, at the present time there is no disease-modifying drug for AD. There is increasing evidence supporting the role of lipid changes in the process of normal cognitive aging and in the etiology of age-related neurodegenerative diseases. AD is characterized by the presence of intraneuronal protein clusters and extracellular aggregates of β-amyloid (Aβ). Disrupted Aβ kinetics may activate intracellular signaling pathways, including ...[more]

PMID: 26538545

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Project description:Acute myocardial infarction (MI) is a cardiovascular disease that remains a major cause of morbidity and mortality worldwide despite advances in its prevention and treatment. During acute myocardial ischemia, the lack of oxygen switches the cell metabolism to anaerobic respiration, with lactate accumulation, ATP depletion, Na+ and Ca2+ overload, and inhibition of myocardial contractile function, which drastically modifies the lipid, protein, and small metabolite profile in the myocardium. Imaging mass spectrometry (IMS) is a powerful technique to comprehensively elucidate the spatial distribution patterns of lipids, peptides, and proteins in biological tissue sections. In this work, we demonstrate an application of multimodal chemical imaging using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), which provided comprehensive molecular information in situ within the same mouse heart tissue sections with myocardial infarction. MALDI-IMS (at 30 μm per pixel) revealed infarct-associated spatial alterations of several lipid species of sphingolipids, glycerophospholipids, lysophospholipids, and cardiolipins along with the acyl carnitines. Further, we performed multimodal MALDI-IMS (IMS3) where dual polarity lipid imaging was combined with subsequent protein MALDI-IMS analysis (at 30 μm per pixel) within the same tissue sections, which revealed accumulations of core histone proteins H4, H2A, and H2B along with post-translational modification products, acetylated H4 and H2A, on the borders of the infarcted region. This methodology allowed us to interpret the lipid and protein molecular pathology of the very same infarcted region in a mouse model of myocardial infarction. Therefore, the presented data highlight the potential of multimodal MALDI imaging mass spectrometry of the same tissue sections as a powerful approach for simultaneous investigation of spatial infarct-associated lipid and protein changes of myocardial infarction.

Dataset Information

Global changes of phospholipids identified by MALDI imaging mass spectrometry in a mouse model of Alzheimer's disease.

Publications

Global changes of phospholipids identified by MALDI imaging mass spectrometry in a mouse model of Alzheimer's disease.

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