Abstract
Alterations in the long chain base of the sphingosine moiety of gangliosides have been shown to play a role in neurodevelopment and neurodegeneration. Indeed, the accumulation of d20:1 sphingosine has been referred to as a metabolic marker of aging in the brain, however, this remains to be shown in simple gangliosides GM2 and GM3. In this study, Matrix-assisted laser desorption/ionization Imaging Mass Spectrometry (MALDI IMS) was used to examine the neuroanatomical distribution of A-series gangliosides with either 18 or 20 carbon sphingosine chains (d18:1 or d20:1) in Fisher 344 rats across the lifespan. The ratio of d20:1/d18:1 species was determined across 11 regions of interest in the brain. Interestingly, a decrease in the d20:1/d18:1 ratio for GM2 and GM3 was observed during early development with the exception of the peri-ventricular corpus callosum, where an age-dependent increase was observed for ganglioside GM3. An age-dependent increase in d20:1 species was confirmed for complex gangliosides GM1 and GD1 with the most significant increase during early development and a high degree of anatomical heterogeneity during aging. The unique neuroanatomically-specific responses of d20:1 ganglioside abundance may lead to a better understanding of regional vulnerability to damage in the aging brain.
Highlights
Gangliosides are a class of glycosphingolipids that are found throughout all cells of the body, with certain species enriched in the central nervous system (CNS)
Gangliosides are structurally composed of a hydrophilic domain, containing sialic acid residues attached to an oligosaccharide chain, along with a hydrophobic domain made up of a ceramide complex (Fig. 1A)
long-chain base (LCB) Genotype differences between Wt and Tg APP21 rats were restricted to GM3 within the peri-ventricular corpus callosum
Summary
Gangliosides are a class of glycosphingolipids that are found throughout all cells of the body, with certain species enriched in the central nervous system (CNS). The literature on this topic has focused almost exclusively on major complex gangliosides GM1, GD1, GT1, and GQ1, with minimal neuroanatomically-specific information, and has not described how the LCB of minor, simple gangliosides shift during aging This information may be crucial as there is increasing evidence pointing to the potential role of simple ganglioside, such as GM3 and GM2, in the development and pathogenesis of neurodegenerative diseases and injuries[7,8,9], the role of the ceramide moiety remains unclear due to technical challenges in the detection of these low abundance species. Previous investigations have used Matrix Assisted Laser Desorption Ionization Imaging Mass Spectrometry (MALDI-IMS) to visualize d18:1 and d20:1 species of ganglioside GM17,8,20,24 This technique has the advantage of simultaneously detecting multiple species of gangliosides (and other molecules) within the same sample based on their abundance and neuroanatomical location. The following study provides the first detailed examination of age-dependent changes in the LCB of both simple and complex A-series gangliosides across a large number brain regions in wildtype (Wt) and APP21 transgenic (Tg) Fisher 344 rats that contain the human mutations to the amyloid precursor protein[24,25]
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