Abstract

Gangliosides are a family of complex lipids that are abundant in the brain. There is no doubt the investigations about the distribution of gangliosides in brian and the relationship between gangliosides and Alzheimer’s disease is profound. However, these investigations are full of challenges due to the structural complexity of gangliosides. In this work, the method for efficient extraction and enrichment of gangliosides from brain was established. Moreover, the distribution of gangliosides in brain was obtained by matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI). It was found that 3-aminoquinoline (3-AQ) as matrix was well-suited for MALDI MS analysis of gangliosides in negative ion mode. In addition, the pretreatment by ethanol (EtOH) cleaning brain section and the addition of ammonium formate greatly improved the MS signal of gangliosides in the brain section when MALDI MSI analysis was employed. The distribution of ganliosides in cerebral cortex, hippocampus and cerebellum was respectively acquired by electrospray ionization (ESI) MS and MALDI MSI, and the data were compared for reliability evaluation of MALDI MSI. Further, applying MALDI MSI technology, the distribution of gangliosides in amyloid precursor protein transgenic mouse brain was obtained, which may provide a new insight for bioresearch of Alzheimer’s disease (AD).

Highlights

  • In April 2013, President Obama unveiled the “BRAIN” Initiative, which was expected to uncover the mysteries of brain disorders, such as Alzheimer’s and Parkinson’s diseases, depression, post-traumatic stress disorder, and traumatic brain injury

  • These results were consistent with those obtained by ultra high performance liquid chromatography (UHPLC)-electrospray ionization (ESI)-FTICR Mass spectrometry (MS), suggesting that the data obtained by matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI) was reliable

  • The sample preparation was optimized for MALDI MSI analysis, and it was found that 3-AQ (30 mg/mL)/ammonium formate (125 mM) as the matrix, and pretreatment by EtOH cleaning brain section could be used for MALDI MSI analysis of ganglioside in brain section

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Summary

Introduction

In April 2013, President Obama unveiled the “BRAIN” Initiative, which was expected to uncover the mysteries of brain disorders, such as Alzheimer’s and Parkinson’s diseases, depression, post-traumatic stress disorder, and traumatic brain injury. Mass spectrometry (MS), cannot be directly used in the study of living body, play a crucial role in the measurement of molecular weight, identification of structure, and analysis of component change, and will provide great help for brain research. In AD, a complex of GM1 (one subclass of ganglioside) and amyloid β -protein (Aβ ) termed “GAβ ,” has been found to accumulate in brain[5] These studies show that it is of great significance to develop reliable bioanalytical methods to measure ganglioside in the brain. Taki established a method for transferring lipids separated on a TLC-plate to a poly-vinylidene difluoride (PVDF) membrane and direct mass spectrometric analysis of ganglioside molecular species from the human brain by MALDI MS13. We constructed a workflow, by combination ESI with MALDI mass spectrometry, for qualitative, semi-quantitative and in situ analysis of gangliosides in brain. We expect to maximize the advantages of each ionization method

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