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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.


Chemical structure of GM1 d18:1 (A, top) and GM1 d20:1 (A, bottom). Mass spectra in the GM1 m/z range generated from two different anatomical regions, the piriform cortex and the striatum, show differential expression of GM1d18:1 and GM1d20:1. (B) The spectrum shown in red has been shifted to the right for better visualization of differences in peaks. Molecular image shows expression of GM1d18:1. For all analyses, the area under the curve (AUC) was calculated for the highest peak of each species (arrows).
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Figure 1: Chemical structure of GM1 d18:1 (A, top) and GM1 d20:1 (A, bottom). Mass spectra in the GM1 m/z range generated from two different anatomical regions, the piriform cortex and the striatum, show differential expression of GM1d18:1 and GM1d20:1. (B) The spectrum shown in red has been shifted to the right for better visualization of differences in peaks. Molecular image shows expression of GM1d18:1. For all analyses, the area under the curve (AUC) was calculated for the highest peak of each species (arrows).

Mentions: Gangliosides are sialylated glycosphingolipids composed of a hydrophobic ceramide base anchored within the cellular membrane and a carbohydrate moiety that extends into the extracellular space (Figure 1A). Gangliosides are highly clustered within lipid rafts, specialized membrane microdomains where signaling molecules are abundant and where the lipid composition can greatly influence the accessibility of proteins involved in signal transduction and cell metabolism (Sonnino et al., 1990; Sonnino and Prinetti, 2010). It is therefore not surprising that gangliosides are especially prominent in brain tissue, accounting for about ten percent of the brain’s lipid mass. Among gangliosides, GM1 is highly expressed within the brain and is known to be involved in a number of neuronal functions, including neuronal differentiation, survival, neurotransmission and neuritogenesis (Posse de Chaves and Sipione, 2010; Ledeen and Wu, 2015). Interest in GM1 has peaked in recent years for its therapeutic potential in neurodegenerative conditions, namely Huntington’s disease (Maglione et al., 2010; Di Pardo et al., 2012) and Parkinson’s disease (Schneider et al., 2010). Yet, there is also a substantial body of evidence linking GM1 to the production of amyloid beta fibrils in Alzheimer’s disease (Ueno et al., 2014; Yanagisawa, 2015).


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)

Chemical structure of GM1 d18:1 (A, top) and GM1 d20:1 (A, bottom). Mass spectra in the GM1 m/z range generated from two different anatomical regions, the piriform cortex and the striatum, show differential expression of GM1d18:1 and GM1d20:1. (B) The spectrum shown in red has been shifted to the right for better visualization of differences in peaks. Molecular image shows expression of GM1d18:1. For all analyses, the area under the curve (AUC) was calculated for the highest peak of each species (arrows).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664653&req=5

Figure 1: Chemical structure of GM1 d18:1 (A, top) and GM1 d20:1 (A, bottom). Mass spectra in the GM1 m/z range generated from two different anatomical regions, the piriform cortex and the striatum, show differential expression of GM1d18:1 and GM1d20:1. (B) The spectrum shown in red has been shifted to the right for better visualization of differences in peaks. Molecular image shows expression of GM1d18:1. For all analyses, the area under the curve (AUC) was calculated for the highest peak of each species (arrows).
Mentions: Gangliosides are sialylated glycosphingolipids composed of a hydrophobic ceramide base anchored within the cellular membrane and a carbohydrate moiety that extends into the extracellular space (Figure 1A). Gangliosides are highly clustered within lipid rafts, specialized membrane microdomains where signaling molecules are abundant and where the lipid composition can greatly influence the accessibility of proteins involved in signal transduction and cell metabolism (Sonnino et al., 1990; Sonnino and Prinetti, 2010). It is therefore not surprising that gangliosides are especially prominent in brain tissue, accounting for about ten percent of the brain’s lipid mass. Among gangliosides, GM1 is highly expressed within the brain and is known to be involved in a number of neuronal functions, including neuronal differentiation, survival, neurotransmission and neuritogenesis (Posse de Chaves and Sipione, 2010; Ledeen and Wu, 2015). Interest in GM1 has peaked in recent years for its therapeutic potential in neurodegenerative conditions, namely Huntington’s disease (Maglione et al., 2010; Di Pardo et al., 2012) and Parkinson’s disease (Schneider et al., 2010). Yet, there is also a substantial body of evidence linking GM1 to the production of amyloid beta fibrils in Alzheimer’s disease (Ueno et al., 2014; Yanagisawa, 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.