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Elevated xCT expression levels in normal appearing white matter of multiple sclerosis patients: a protective mechanism or a trigger for excitotoxic damage? / Merckx, Ellen; Jensen, Cathy; Paterka, Magdalena; Bentea, Eduard-Mihai; Van Liefferinge, Joeri; Demuyser, Thomas; Smolders, Ilse Julia; Van Loo, Geert; De Keyser, Jacques; Rombaut, Bartholomeus; Sato, Hideyo; Methner, Axel; Michiels, Thomas; Massie, Ann.

10th bi-annual meeting of the Belgian Society for Neuroscience (BSN), Brussels, May 31, 2013. 2013.

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Merckx, E, Jensen, C, Paterka, M, Bentea, E-M, Van Liefferinge, J, Demuyser, T, Smolders, IJ, Van Loo, G, De Keyser, J, Rombaut, B, Sato, H, Methner, A, Michiels, T & Massie, A 2013, Elevated xCT expression levels in normal appearing white matter of multiple sclerosis patients: a protective mechanism or a trigger for excitotoxic damage? in 10th bi-annual meeting of the Belgian Society for Neuroscience (BSN), Brussels, May 31, 2013. 10th bi-annual meeting of the Belgian Society for Neuroscience, Jette, Belgium, 31/05/13.

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@inbook{71a47d7c0c904cdca98f81f0890d4515,
title = "Elevated xCT expression levels in normal appearing white matter of multiple sclerosis patients: a protective mechanism or a trigger for excitotoxic damage?",
abstract = "Multiple sclerosis (MS) is one of the most frequent disorders of the central nervous system. Excitotoxicity as well as oxidative stress are part of the pathogenesis, in accordance to other neurological diseases. The cystine/glutamate antiporter or system xc-, with xCT as specific subunit, imports cystine in exchange for glutamate and can as such affect intracellular antioxidant as well as extracellular glutamate levels. Oxidative stress induces the expression of xCT and could consequently aggravate excitotoxic damage. We found increased xCT protein expression levels in the normal appearing white matter of MS patients compared to healthy controls, suggesting an involvement of system xc- in the pathogenesis of MS. However, in an animal model for MS, i.e. the TMEV (Theiler's murine encephalomyelitis virus) mouse model, we could not observe any effect on xCT expression in spinal cord. Also in vitro, TMEV infection of macrophages could not affect xCT expression or system xc- activity. We next compared the susceptibility of xCT-/- mice in the EAE (experimental autoimmune encephalomyelitis) model to wildtype littermates. No significant difference could be observed in the appearance of the clinical signs between both genotypes. Current experiments will reveal whether a restricted loss of system xc- (i.e. only in immune cells while brain levels remain unaffected) could protect against EAE-induced symptoms/damage. We hypothesize that the infiltrating immune cells could induce excitotoxic damage in the spinal cord as it has been shown that xCT expression is increased in these cells as well as in the spleen (contrary to brain) after EAE induction.",
keywords = "cystine/glutamate antiporter",
author = "Ellen Merckx and Cathy Jensen and Magdalena Paterka and Eduard-Mihai Bentea and {Van Liefferinge}, Joeri and Thomas Demuyser and Smolders, {Ilse Julia} and {Van Loo}, Geert and {De Keyser}, Jacques and Bartholomeus Rombaut and Hideyo Sato and Axel Methner and Thomas Michiels and Ann Massie",
year = "2013",
month = "5",
day = "31",
language = "English",
booktitle = "10th bi-annual meeting of the Belgian Society for Neuroscience (BSN), Brussels, May 31, 2013",

}

RIS

TY - CHAP

T1 - Elevated xCT expression levels in normal appearing white matter of multiple sclerosis patients: a protective mechanism or a trigger for excitotoxic damage?

AU - Merckx, Ellen

AU - Jensen, Cathy

AU - Paterka, Magdalena

AU - Bentea, Eduard-Mihai

AU - Van Liefferinge, Joeri

AU - Demuyser, Thomas

AU - Smolders, Ilse Julia

AU - Van Loo, Geert

AU - De Keyser, Jacques

AU - Rombaut, Bartholomeus

AU - Sato, Hideyo

AU - Methner, Axel

AU - Michiels, Thomas

AU - Massie, Ann

PY - 2013/5/31

Y1 - 2013/5/31

N2 - Multiple sclerosis (MS) is one of the most frequent disorders of the central nervous system. Excitotoxicity as well as oxidative stress are part of the pathogenesis, in accordance to other neurological diseases. The cystine/glutamate antiporter or system xc-, with xCT as specific subunit, imports cystine in exchange for glutamate and can as such affect intracellular antioxidant as well as extracellular glutamate levels. Oxidative stress induces the expression of xCT and could consequently aggravate excitotoxic damage. We found increased xCT protein expression levels in the normal appearing white matter of MS patients compared to healthy controls, suggesting an involvement of system xc- in the pathogenesis of MS. However, in an animal model for MS, i.e. the TMEV (Theiler's murine encephalomyelitis virus) mouse model, we could not observe any effect on xCT expression in spinal cord. Also in vitro, TMEV infection of macrophages could not affect xCT expression or system xc- activity. We next compared the susceptibility of xCT-/- mice in the EAE (experimental autoimmune encephalomyelitis) model to wildtype littermates. No significant difference could be observed in the appearance of the clinical signs between both genotypes. Current experiments will reveal whether a restricted loss of system xc- (i.e. only in immune cells while brain levels remain unaffected) could protect against EAE-induced symptoms/damage. We hypothesize that the infiltrating immune cells could induce excitotoxic damage in the spinal cord as it has been shown that xCT expression is increased in these cells as well as in the spleen (contrary to brain) after EAE induction.

AB - Multiple sclerosis (MS) is one of the most frequent disorders of the central nervous system. Excitotoxicity as well as oxidative stress are part of the pathogenesis, in accordance to other neurological diseases. The cystine/glutamate antiporter or system xc-, with xCT as specific subunit, imports cystine in exchange for glutamate and can as such affect intracellular antioxidant as well as extracellular glutamate levels. Oxidative stress induces the expression of xCT and could consequently aggravate excitotoxic damage. We found increased xCT protein expression levels in the normal appearing white matter of MS patients compared to healthy controls, suggesting an involvement of system xc- in the pathogenesis of MS. However, in an animal model for MS, i.e. the TMEV (Theiler's murine encephalomyelitis virus) mouse model, we could not observe any effect on xCT expression in spinal cord. Also in vitro, TMEV infection of macrophages could not affect xCT expression or system xc- activity. We next compared the susceptibility of xCT-/- mice in the EAE (experimental autoimmune encephalomyelitis) model to wildtype littermates. No significant difference could be observed in the appearance of the clinical signs between both genotypes. Current experiments will reveal whether a restricted loss of system xc- (i.e. only in immune cells while brain levels remain unaffected) could protect against EAE-induced symptoms/damage. We hypothesize that the infiltrating immune cells could induce excitotoxic damage in the spinal cord as it has been shown that xCT expression is increased in these cells as well as in the spleen (contrary to brain) after EAE induction.

KW - cystine/glutamate antiporter

M3 - Meeting abstract (Book)

BT - 10th bi-annual meeting of the Belgian Society for Neuroscience (BSN), Brussels, May 31, 2013

ER -

ID: 2377396