Imaging Mass Spectrometry Technology and Application on Ganglioside Study; Visualization of Age-Dependent Accumulation of C20-Ganglioside Molecular Species in the Mouse Hippocampus

Abstract

Gangliosides are particularly abundant in the central nervous system (CNS) and thought to play important roles in memory formation, neuritogenesis, synaptic transmission, and other neural functions. Although several molecular species of gangliosides have been characterized and their individual functions elucidated, their differential distribution in the CNS are not well understood. In particular, whether the different molecular species show different distribution patterns in the brain remains unclear. We report the distinct and characteristic distributions of ganglioside molecular species, as revealed by imaging mass spectrometry (IMS). This technique can discriminate the molecular species, raised from both oligosaccharide and ceramide structure by determining the difference of the mass-to-charge ratio, and structural analysis by tandem mass spectrometry. Gangliosides in the CNS are characterized by the structure of the long-chain base (LCB) in the ceramide moiety. The LCB of the main ganglioside species has either 18 or 20 carbons (i.e., C18- or C20-sphingosine); we found that these 2 types of gangliosides are differentially distributed in the mouse brain. While the C18-species was widely distributed throughout the frontal brain, the C20-species selectively localized along the entorhinal-hippocampus projections, especially in the molecular layer (ML) of the dentate gyrus (DG). We revealed development- and aging-related accumulation of the C-20 species in the ML-DG. Thus it is possible to consider that this brain-region specific regulation of LCB chain length is particularly important for the distinct function in cells of CNS.

Visualization of lipids in skeletal muscles by mass spectrometry imaging

“…1). MALDI-MSI is applicable for the visualization of a wide range of biomolecules such as lipids 9,10) , glycolipids 11,12) , and proteins 13) , as well as nutrients 14,15) . This imaging modality is expected to be a suitable tool for investigating the pathologic conditions of different muscle groups.…”

Imaging mass spectrometry: principle and application

“…In contrast, the concentration of the C-18 species decreased in the molecular layer (ML)/SLM with aging (arrows). Reprinted from Sugiura et al (2008) pons/medullar pons/medullary PCA provides information regarding which molecules are altered in tissue microdomains and is very helpful in analyzing large datasets of imaging MS (Altelaar et al 2007;Denkert et al 2006;Lapolla et al 2007;McCombie et al 2005;Zaima et al 2009b).…”

Current Imaging Mass Spectrometry for Metabolite Molecules

“…While the C18 species is widely distributed throughout the frontal brain, the C20 species is selectively localized in specific brain regions, namely, in the molecular layer (ML) of the dentate gyrus (DG). Furthermore, the developmental-and aging-related accumulation of the C20 species in the ML-DG can be visualized, 15) i.e., we could specify the tissue location where C20 gangliosides accumulate (Fig. 7).…”