Differential Anatomical Expression of Ganglioside GM1 Species Containing d18:1 or d20:1 Sphingosine Detected by MALDI Imaging Mass Spectrometry in Mature Rat Brain

Abstract

GM1 ganglioside plays a role in essential neuronal processes, including differentiation, survival, and signaling. Yet, little is known about GM1 species with different sphingosine bases, such as the most abundant species containing 18 carbon atoms in the sphingosine chain (GM1d18:1), and the less abundant containing 20 carbon atoms (GM1d20:1). While absent in the early fetal brain, GM1d20:1 continues to increase throughout pre- and postnatal development and into old age, raising questions about the functional relevance of the GM1d18:1 to GM1d20:1 ratio. Matrix-assisted laser desorption/ionization imaging mass spectrometry is a novel technology that allows differentiation between these two GM1 species and quantification of their expression within an anatomical context. Using this technology, we find GM1d18:1/d20:1 expression ratios are highly specific to defined anatomical brain regions in adult rats. Thus, the ratio was significantly different among different thalamic nuclei and between the corpus callosum and internal capsule. Differential GM1d18:1/GM1d20:1 ratios measured in hippocampal subregions in rat brain complement previous studies conducted in mice. Across layers of the sensory cortex, opposing expression gradients were found for GM1d18:1 and GM1d20:1. Superficial layers demonstrated lower GM1d18:1 and higher GM1d20:1 signal than other layers, while in deep layers GM1d18:1 expression was relatively high and GM1d20:1 expression low. By far the highest GM1d18:1/d20:1 ratio was found in the amygdala. Differential expression of GM1 with d18:1- or d20:1-sphingosine bases in the adult rat brain suggests tight regulation of expression and points toward a distinct functional relevance for each of these GM1 species in neuronal processes.

Mechanisms of lysophosphatidylcholine‐induced demyelination: A primary lipid disrupting myelinopathy

“…Image mass spectrometry was conducted similar to before (Weishaupt, Caughlin, Yeung, & Whitehead, 2015). Molecular images were analyzed using Tissue View Software (Sciex).…”

Age-dependent and regional heterogeneity in the long-chain base of A-series gangliosides observed in the rat brain using MALDI Imaging

“…Previous investigations have used Matrix Assisted Laser Desorption Ionization Imaging Mass Spectrometry (MALDI-IMS) to visualize d18:1 and d20:1 species of ganglioside GM1 7 , 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.…”

“…A study describing the expression of d18:1 and d20:1 species of all A-series gangliosides during the aging process has not yet been done. Therefore, 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 . We hypothesized that there would be significant regional differences in the ratio of d20:1 species relative to d18:1 across the brain throughout aging and that this would be enhanced in the Tg APP21 rat.…”

MALDI imaging delineates hippocampal glycosphingolipid changes associated with neurotoxin induced proteopathy following neonatal BMAA exposure

“…The key strength of IMS compared to common imaging techniques is the ability to provide spatial localization of chemical species together with quantitative estimates as particularly illustrated previously for ganglioside species in the brain [24–26]. Similarly, the distribution of various gangliosides in rodent brain has been reported in other recent studies [50–52]. Here, a characteristic increase of cortical GM2 and GM3 levels was reported in a Hunter’s disease (HD) mouse model [53].…”