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Amyotrophic lateral sclerosis and denervation alter sphingolipids and up-regulate glucosylceramide synthase.

Henriques A, Croixmarie V, Priestman DA, Rosenbohm A, Dirrig-Grosch S, D'Ambra E, Huebecker M, Hussain G, Boursier-Neyret C, Echaniz-Laguna A, Ludolph AC, Platt FM, Walther B, Spedding M, Loeffler JP, Gonzalez De Aguilar JL - Hum. Mol. Genet. (2015)

Bottom Line: Significant changes in lipid expression were evident in spinal cord and skeletal muscle before overt neuropathology.In silico analysis also revealed appreciable changes in sphingolipids including ceramides and glucosylceramides (GlcCer).HPLC analysis showed increased amounts of GlcCer and downstream glycosphingolipids (GSLs) in SOD1(G86R) muscle compared with wild-type littermates.

View Article: PubMed Central - PubMed

Affiliation: Université de Strasbourg, UMR_S 1118, Strasbourg, France, INSERM, U1118, Mécanismes Centraux et Péripheriques de la Neurodégénérescence, Strasbourg, France.

No MeSH data available.


Related in: MedlinePlus

Lipidomic signatures in spinal cord and muscle of SOD1(G86R) mice. PCA (A and C) and PLS-DA (B and D) score plots showing the spatial distribution of SOD1(G86R) mice at the pre-symptomatic stage (blue circles, n = 9) and WT littermates (red circles, n = 9), according to the lipidomic profiles of spinal cord (A and B) and muscle (C and D).
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DDV439F1: Lipidomic signatures in spinal cord and muscle of SOD1(G86R) mice. PCA (A and C) and PLS-DA (B and D) score plots showing the spatial distribution of SOD1(G86R) mice at the pre-symptomatic stage (blue circles, n = 9) and WT littermates (red circles, n = 9), according to the lipidomic profiles of spinal cord (A and B) and muscle (C and D).

Mentions: We studied differences in the lipidomes of wild-type (WT) and SOD1(G86R) mice at pre-symptomatic and symptomatic ages (Supplementary Material, Fig. S1). Unsupervised principal component analysis (PCA) of spinal cord and muscle samples revealed two clusters of individuals, corresponding to WT and SOD1(G86R) mice, respectively, that were clearly distinguishable even at the pre-symptomatic stage. We also performed partial least-squares discriminant analysis, which is a supervised alternative to differentiate between experimental groups. This analysis revealed lipid changes in spinal cord and muscle, which significantly distinguished SOD1(G86R) mice from WT littermates at the pre-symptomatic stage (Fig. 1). Very similar results were obtained with samples from symptomatic mice (Supplementary Material, Fig. S2). In spinal cord of pre-symptomatic and symptomatic mice, most lipids, which were affected, were decreased. In contrast, most of the lipids with significant changes in muscle of SOD1(G86R) mice were increased (Table 1).Table 1.


Amyotrophic lateral sclerosis and denervation alter sphingolipids and up-regulate glucosylceramide synthase.

Henriques A, Croixmarie V, Priestman DA, Rosenbohm A, Dirrig-Grosch S, D'Ambra E, Huebecker M, Hussain G, Boursier-Neyret C, Echaniz-Laguna A, Ludolph AC, Platt FM, Walther B, Spedding M, Loeffler JP, Gonzalez De Aguilar JL - Hum. Mol. Genet. (2015)

Lipidomic signatures in spinal cord and muscle of SOD1(G86R) mice. PCA (A and C) and PLS-DA (B and D) score plots showing the spatial distribution of SOD1(G86R) mice at the pre-symptomatic stage (blue circles, n = 9) and WT littermates (red circles, n = 9), according to the lipidomic profiles of spinal cord (A and B) and muscle (C and D).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664174&req=5

DDV439F1: Lipidomic signatures in spinal cord and muscle of SOD1(G86R) mice. PCA (A and C) and PLS-DA (B and D) score plots showing the spatial distribution of SOD1(G86R) mice at the pre-symptomatic stage (blue circles, n = 9) and WT littermates (red circles, n = 9), according to the lipidomic profiles of spinal cord (A and B) and muscle (C and D).
Mentions: We studied differences in the lipidomes of wild-type (WT) and SOD1(G86R) mice at pre-symptomatic and symptomatic ages (Supplementary Material, Fig. S1). Unsupervised principal component analysis (PCA) of spinal cord and muscle samples revealed two clusters of individuals, corresponding to WT and SOD1(G86R) mice, respectively, that were clearly distinguishable even at the pre-symptomatic stage. We also performed partial least-squares discriminant analysis, which is a supervised alternative to differentiate between experimental groups. This analysis revealed lipid changes in spinal cord and muscle, which significantly distinguished SOD1(G86R) mice from WT littermates at the pre-symptomatic stage (Fig. 1). Very similar results were obtained with samples from symptomatic mice (Supplementary Material, Fig. S2). In spinal cord of pre-symptomatic and symptomatic mice, most lipids, which were affected, were decreased. In contrast, most of the lipids with significant changes in muscle of SOD1(G86R) mice were increased (Table 1).Table 1.

Bottom Line: Significant changes in lipid expression were evident in spinal cord and skeletal muscle before overt neuropathology.In silico analysis also revealed appreciable changes in sphingolipids including ceramides and glucosylceramides (GlcCer).HPLC analysis showed increased amounts of GlcCer and downstream glycosphingolipids (GSLs) in SOD1(G86R) muscle compared with wild-type littermates.

View Article: PubMed Central - PubMed

Affiliation: Université de Strasbourg, UMR_S 1118, Strasbourg, France, INSERM, U1118, Mécanismes Centraux et Péripheriques de la Neurodégénérescence, Strasbourg, France.

No MeSH data available.


Related in: MedlinePlus