xCT protein is the specific subunit of System xc-, a multi-proteic complex importing cystine into cell while releasing extracellular glutamate. Although xCT protein expression is detected in brain glial cells, its expression in the spinal cord and during spinal cord disorders remain elusive. The aim of this study is to characterize the contribution of xCT to functional and histological outcomes following SCI, using wild-type mice (xCT+/+) and genetically-invalidated mice (xCT-/-). In situ hybridization allowed to detect xCT mRNA mostly in astrocyte subpopulations and in meningeal fibroblasts in the normal spinal cord. During the subacute phase of spinal cord injury, xCT mRNA could also be detected in significant amount in microglial cells. Moreover, overall xCT mRNA levels were upregulated, peaking at 4 days post-injury. While both injured xCT+/+ and xCT-/- mice recovered partly their motor functions, xCT-/- mice recovered muscular grip strength as well as pre-SCI weight substantially faster than xCT+/+ mice. Histology of injured spinal cords revealed increased number of motor neurons in xCT-/- mice at multiple distances around lesion epicenter. Intraspinal glutathione levels were unchanged in both injured groups. As xCT has been demonstrated as a regulator of microglial function (Mesci et al., Brain, 2015), we assessed markers of microglial activation. At 2 weeks post-SCI, the number of type A Iba1+ cells was unexpectedly much higher in contused xCT-/- than in xCT+/+ spinal cords. Analysis of M1/M2 polarization showed that contused xCT-/- spinal cords contained higher mRNA levels of Ym1 and IGF-1 (M2) while lower levels of NOX2 and TNF-a (M1). Additionally, the number of reactive astrocytes was slightly higher in xCT-/- mice. The number of surviving oligodendrocytes was unchanged between the two injured groups. This study suggests that, following SCI trauma, an early xCT upregulation (if confirmed at the protein level) is detrimental to motor neuron survival and influences inflammation by dysbalancing M1/M2 polarization.
|Title of host publication||Front. Neurosci. Conference Abstract: 13th Nat. Congress of the Belgian Society of Neuroscience, May 24, 2019, Royal Academy Brussels|
|Number of pages||1|
|Publication status||Published - 2 May 2019|
|Event||Federation of European Neuroscience Societies - FENS: 13th National Congress of the BSN - Royal Academy Brussels, Belgium|
Duration: 24 May 2019 → …
|Conference||Federation of European Neuroscience Societies - FENS|
|Period||24/05/19 → …|