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

Weishaupt N, Caughlin S, Yeung KK, Whitehead SN - Front Neuroanat (2015)

Bottom Line: Across layers of the sensory cortex, opposing expression gradients were found for GM1d18:1 and GM1d20:1.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London ON, Canada.

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.

No MeSH data available.


Sampling regions for the DMN included its lateral and medial parts, the ROI covering the VPM may also have included parts of the VPL (A). CM, central medial thalamic nucleus; LPMR, lateral posterior thalamic nucleus, mediorostral part; MDL, mediodorsal thalamic nucleus, lateral part; MDM, mediodorsal thalamic nucleus, medial part; VPL, ventral posterolateral thalamic nucleus; VPM, ventral posteromedial thalamic nucleus. Molecular images of GM1d18:1 expression (green) and GM1d20:1 expression (red) showed differential expression of the two species within the DMN and VPM, as well as within the LPMR (not quantified, B). Scale bar = 1 mm. The ratio of GM1d18:1/GM1d20:1 was significantly higher within the DMN than the VPM (Mann–Whitney test, ∗∗∗∗p < 0.0001, C).
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Figure 5: Sampling regions for the DMN included its lateral and medial parts, the ROI covering the VPM may also have included parts of the VPL (A). CM, central medial thalamic nucleus; LPMR, lateral posterior thalamic nucleus, mediorostral part; MDL, mediodorsal thalamic nucleus, lateral part; MDM, mediodorsal thalamic nucleus, medial part; VPL, ventral posterolateral thalamic nucleus; VPM, ventral posteromedial thalamic nucleus. Molecular images of GM1d18:1 expression (green) and GM1d20:1 expression (red) showed differential expression of the two species within the DMN and VPM, as well as within the LPMR (not quantified, B). Scale bar = 1 mm. The ratio of GM1d18:1/GM1d20:1 was significantly higher within the DMN than the VPM (Mann–Whitney test, ∗∗∗∗p < 0.0001, C).

Mentions: The thalamus is a highly diverse structure that offers a multitude of regions for analysis of GM1 expression. Because we can sample areas that are visibly delineated by their GM1d18:1 or GM1d20:2 expression profile with the highest confidence, we chose the DMN and the ventral posteromedial nucleus (VPM) of the thalamus for analysis (Figure 5A). While the DMN demonstrated high GM1d18:1 signal intensity in molecular images, hardly any GM1d20:1 signal could be observed visually (Figure 5B). Both species were expressed at relatively low levels in the VPM, leading to a significantly higher GM1d18:1/GM1d20:1 ratio in the DMN (4.53 ± 0.12, n = 18) versus the VPM (3.14 ± 0.13, n = 18, Mann–Whitney test, p < 0.0001, Figure 5C). Differential expression was also observed within the lateral posterior thalamic nucleus (Figures 5A,B, not quantified).


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

Weishaupt N, Caughlin S, Yeung KK, Whitehead SN - Front Neuroanat (2015)

Sampling regions for the DMN included its lateral and medial parts, the ROI covering the VPM may also have included parts of the VPL (A). CM, central medial thalamic nucleus; LPMR, lateral posterior thalamic nucleus, mediorostral part; MDL, mediodorsal thalamic nucleus, lateral part; MDM, mediodorsal thalamic nucleus, medial part; VPL, ventral posterolateral thalamic nucleus; VPM, ventral posteromedial thalamic nucleus. Molecular images of GM1d18:1 expression (green) and GM1d20:1 expression (red) showed differential expression of the two species within the DMN and VPM, as well as within the LPMR (not quantified, B). Scale bar = 1 mm. The ratio of GM1d18:1/GM1d20:1 was significantly higher within the DMN than the VPM (Mann–Whitney test, ∗∗∗∗p < 0.0001, C).
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Figure 5: Sampling regions for the DMN included its lateral and medial parts, the ROI covering the VPM may also have included parts of the VPL (A). CM, central medial thalamic nucleus; LPMR, lateral posterior thalamic nucleus, mediorostral part; MDL, mediodorsal thalamic nucleus, lateral part; MDM, mediodorsal thalamic nucleus, medial part; VPL, ventral posterolateral thalamic nucleus; VPM, ventral posteromedial thalamic nucleus. Molecular images of GM1d18:1 expression (green) and GM1d20:1 expression (red) showed differential expression of the two species within the DMN and VPM, as well as within the LPMR (not quantified, B). Scale bar = 1 mm. The ratio of GM1d18:1/GM1d20:1 was significantly higher within the DMN than the VPM (Mann–Whitney test, ∗∗∗∗p < 0.0001, C).
Mentions: The thalamus is a highly diverse structure that offers a multitude of regions for analysis of GM1 expression. Because we can sample areas that are visibly delineated by their GM1d18:1 or GM1d20:2 expression profile with the highest confidence, we chose the DMN and the ventral posteromedial nucleus (VPM) of the thalamus for analysis (Figure 5A). While the DMN demonstrated high GM1d18:1 signal intensity in molecular images, hardly any GM1d20:1 signal could be observed visually (Figure 5B). Both species were expressed at relatively low levels in the VPM, leading to a significantly higher GM1d18:1/GM1d20:1 ratio in the DMN (4.53 ± 0.12, n = 18) versus the VPM (3.14 ± 0.13, n = 18, Mann–Whitney test, p < 0.0001, Figure 5C). Differential expression was also observed within the lateral posterior thalamic nucleus (Figures 5A,B, not quantified).

Bottom Line: Across layers of the sensory cortex, opposing expression gradients were found for GM1d18:1 and GM1d20:1.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London ON, Canada.

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.

No MeSH data available.