Cystine–glutamate antiporter deletion accelerates motor recovery and improves histological outcomes following spinal cord injury in mice

Abstract xCT is the specific subunit of System xc-, an antiporter importing cystine while releasing glutamate. Although xCT expression has been found in the spinal cord, its expression and role after spinal cord injury (SCI) remain unknown. The aim of this study was to characterize the role of xCT o...

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Autores principales:	Lindsay Sprimont, Pauline Janssen, Kathleen De Swert, Mathias Van Bulck, Ilse Rooman, Jacques Gilloteaux, Ann Massie, Charles Nicaise
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0c960f346c93467d92befefbdd905a9b
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spelling	oai:doaj.org-article:0c960f346c93467d92befefbdd905a9b2021-12-02T17:30:34ZCystine–glutamate antiporter deletion accelerates motor recovery and improves histological outcomes following spinal cord injury in mice10.1038/s41598-021-91698-y2045-2322https://doaj.org/article/0c960f346c93467d92befefbdd905a9b2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91698-yhttps://doaj.org/toc/2045-2322Abstract xCT is the specific subunit of System xc-, an antiporter importing cystine while releasing glutamate. Although xCT expression has been found in the spinal cord, its expression and role after spinal cord injury (SCI) remain unknown. The aim of this study was to characterize the role of xCT on functional and histological outcomes following SCI induced in wild-type (xCT+/+) and in xCT-deficient mice (xCT−/−). In the normal mouse spinal cord, slc7a11/xCT mRNA was detected in meningeal fibroblasts, vascular mural cells, astrocytes, motor neurons and to a lesser extent in microglia. slc7a11/xCT gene and protein were upregulated within two weeks post-SCI. xCT−/− mice recovered muscular grip strength as well as pre-SCI weight faster than xCT+/+ mice. Histology of xCT−/− spinal cords revealed significantly more spared motor neurons and a higher number of quiescent microglia. In xCT−/− mice, inflammatory polarization shifted towards higher mRNA expression of ym1 and igf1 (anti-inflammatory) while lower levels of nox2 and tnf-a (pro-inflammatory). Although astrocyte polarization did not differ, we quantified an increased expression of lcn2 mRNA. Our results show that slc7a11/xCT is overexpressed early following SCI and is detrimental to motor neuron survival. xCT deletion modulates intraspinal glial activation by shifting towards an anti-inflammatory profile.Lindsay SprimontPauline JanssenKathleen De SwertMathias Van BulckIlse RoomanJacques GilloteauxAnn MassieCharles NicaiseNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lindsay Sprimont Pauline Janssen Kathleen De Swert Mathias Van Bulck Ilse Rooman Jacques Gilloteaux Ann Massie Charles Nicaise Cystine–glutamate antiporter deletion accelerates motor recovery and improves histological outcomes following spinal cord injury in mice
description	Abstract xCT is the specific subunit of System xc-, an antiporter importing cystine while releasing glutamate. Although xCT expression has been found in the spinal cord, its expression and role after spinal cord injury (SCI) remain unknown. The aim of this study was to characterize the role of xCT on functional and histological outcomes following SCI induced in wild-type (xCT+/+) and in xCT-deficient mice (xCT−/−). In the normal mouse spinal cord, slc7a11/xCT mRNA was detected in meningeal fibroblasts, vascular mural cells, astrocytes, motor neurons and to a lesser extent in microglia. slc7a11/xCT gene and protein were upregulated within two weeks post-SCI. xCT−/− mice recovered muscular grip strength as well as pre-SCI weight faster than xCT+/+ mice. Histology of xCT−/− spinal cords revealed significantly more spared motor neurons and a higher number of quiescent microglia. In xCT−/− mice, inflammatory polarization shifted towards higher mRNA expression of ym1 and igf1 (anti-inflammatory) while lower levels of nox2 and tnf-a (pro-inflammatory). Although astrocyte polarization did not differ, we quantified an increased expression of lcn2 mRNA. Our results show that slc7a11/xCT is overexpressed early following SCI and is detrimental to motor neuron survival. xCT deletion modulates intraspinal glial activation by shifting towards an anti-inflammatory profile.
format	article
author	Lindsay Sprimont Pauline Janssen Kathleen De Swert Mathias Van Bulck Ilse Rooman Jacques Gilloteaux Ann Massie Charles Nicaise
author_facet	Lindsay Sprimont Pauline Janssen Kathleen De Swert Mathias Van Bulck Ilse Rooman Jacques Gilloteaux Ann Massie Charles Nicaise
author_sort	Lindsay Sprimont
title	Cystine–glutamate antiporter deletion accelerates motor recovery and improves histological outcomes following spinal cord injury in mice
title_short	Cystine–glutamate antiporter deletion accelerates motor recovery and improves histological outcomes following spinal cord injury in mice
title_full	Cystine–glutamate antiporter deletion accelerates motor recovery and improves histological outcomes following spinal cord injury in mice
title_fullStr	Cystine–glutamate antiporter deletion accelerates motor recovery and improves histological outcomes following spinal cord injury in mice
title_full_unstemmed	Cystine–glutamate antiporter deletion accelerates motor recovery and improves histological outcomes following spinal cord injury in mice
title_sort	cystine–glutamate antiporter deletion accelerates motor recovery and improves histological outcomes following spinal cord injury in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0c960f346c93467d92befefbdd905a9b
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Cystine–glutamate antiporter deletion accelerates motor recovery and improves histological outcomes following spinal cord injury in mice

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