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.
Highlights
Gangliosides are glycosphingolipids consisting of mono- to polysialylated oligosaccharide chains of variable lengths attached to a ceramide unit
To confirm that the differences of 28-u which corresponds to a (CH2)2 unit, observed between the C18 and C20 species, can be certainly attributed to the long-chain base (LCB) chain lengths, we performed a structural analysis of ions corresponding to GM1 gangliosides by MSn (Figure 2B)
As a step of the previous study which characterized the distinct composition of ganglioside molecular species between axons/dendrites and soma of neuron in vitro [33], in the present study, we demonstrated that gangliosides with differences in their ceramide moieties showed distinct distribution patterns in the mouse brain, especially in the hippocampal formation in vivo
Summary
Gangliosides are glycosphingolipids consisting of mono- to polysialylated oligosaccharide chains of variable lengths attached to a ceramide unit. They are inserted in the outer layer of the plasma membrane with the hydrophobic ceramide moiety acting as an anchor, while their oligosaccharide moiety is exposed to the external medium[1]. Gangliosides are abundant in the central nervous system (CNS) and are thought to play roles in memory formation[2], neuritogenesis[3], synaptic transmission[4], and other neural functions. They are involved in brain development and maturation[5,6]. The ganglioside GM3 has been found to be closely associated with signaling proteins, such as c-Src, Rho, FAK, and Ras, in cultured cells[3,7,8], and GD3 is associated with the Src-family kinase Lyn and the neural cell adhesion molecule TAG-1 in rat brain[9,10]
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