Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe n...Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe nerve damage.Ferroptosis is an iron-dependent form of regulated cell death caused by membrane rupture induced by lipid peroxidation,and plays an important role in the pathological process of ischemic stroke.However,there are few studies on oligodendrocyte progenitor cell ferroptosis.We analyzed transcriptome sequencing data from GEO databases and identified a role of ferroptosis in oligodendrocyte progenitor cell death and myelin injury after cerebral ischemia.Bioinformatics analysis suggested that perilipin-2(PLIN2)was involved in oligodendrocyte progenitor cell ferroptosis.PLIN2 is a lipid storage protein and a marker of hypoxia-sensitive lipid droplet accumulation.For further investigation,we established a mouse model of cerebral ischemia/reperfusion.We found significant myelin damage after cerebral ischemia,as well as oligodendrocyte progenitor cell death and increased lipid peroxidation levels around the infarct area.The ferroptosis inhibitor,ferrostatin-1,rescued oligodendrocyte progenitor cell death and subsequent myelin injury.We also found increased PLIN2 levels in the peri-infarct area that co-localized with oligodendrocyte progenitor cells.Plin2 knockdown rescued demyelination and improved neurological deficits.Our findings suggest that targeting PLIN2 to regulate oligodendrocyte progenitor cell ferroptosis may be a potential therapeutic strategy for rescuing myelin damage after cerebral ischemia.展开更多
Monocarboxylic acid transporter 1(MCT1)maintains axonal function by transferring lactic acid from oligodendrocytes to axons.Subarachnoid hemorrhage(SAH)induces white matter injury,but the involvement of MCT1 is unclea...Monocarboxylic acid transporter 1(MCT1)maintains axonal function by transferring lactic acid from oligodendrocytes to axons.Subarachnoid hemorrhage(SAH)induces white matter injury,but the involvement of MCT1 is unclear.In this study,the SAH model of adult male Sprague-Dawley rats was used to explore the role of MCT1 in white matter injury after SAH.At 48 h after SAH,oligodendrocyte MCT1 was significantly reduced,and the exogenous overexpression of MCT1 significantly improved white matter integrity and long-term cognitive function.Motor training after SAH significantly increased the number of ITPR2+SOX10+oligodendrocytes and upregulated the level of MCT1,which was positively correlated with the behavioral ability of rats.In addition,miR-29b and miR-124 levels were significantly increased in SAH rats compared with non-SAH rats.Further intervention experiments showed that miR-29b and miR-124 could negatively regulate the level of MCT1.This study confirmed that the loss of MCT1 may be one of the mechanisms of white matter damage after SAH and may be caused by the negative regulation of miR-29b and miR-124.MCT1 may be involved in the neurological improvement of rehabilitation training after SAH.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82071307(to HL),82271362(to HL),82171294(to JW),82371303(to JW),and 82301460(to PX)the Natural Science Foundation of Jiangsu Province,No.BK20211552(to HL)+1 种基金Suzhou Medical Technology Innovation Project-Clinical Frontier,No.SKY2022002(to ZY)the Science and Education Foundation for Health of Suzhou for Youth,No.KJXW2023001(to XL)。
文摘Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe nerve damage.Ferroptosis is an iron-dependent form of regulated cell death caused by membrane rupture induced by lipid peroxidation,and plays an important role in the pathological process of ischemic stroke.However,there are few studies on oligodendrocyte progenitor cell ferroptosis.We analyzed transcriptome sequencing data from GEO databases and identified a role of ferroptosis in oligodendrocyte progenitor cell death and myelin injury after cerebral ischemia.Bioinformatics analysis suggested that perilipin-2(PLIN2)was involved in oligodendrocyte progenitor cell ferroptosis.PLIN2 is a lipid storage protein and a marker of hypoxia-sensitive lipid droplet accumulation.For further investigation,we established a mouse model of cerebral ischemia/reperfusion.We found significant myelin damage after cerebral ischemia,as well as oligodendrocyte progenitor cell death and increased lipid peroxidation levels around the infarct area.The ferroptosis inhibitor,ferrostatin-1,rescued oligodendrocyte progenitor cell death and subsequent myelin injury.We also found increased PLIN2 levels in the peri-infarct area that co-localized with oligodendrocyte progenitor cells.Plin2 knockdown rescued demyelination and improved neurological deficits.Our findings suggest that targeting PLIN2 to regulate oligodendrocyte progenitor cell ferroptosis may be a potential therapeutic strategy for rescuing myelin damage after cerebral ischemia.
基金supported by National Key R&D Program of China(Nos.2018YFC1312600 and 2018YFC1312601)National Natural Science Foundation of China(Nos.81830036,81771254,81771255,81873741,and 82071307)+4 种基金China Postdoctoral Science Foundation(No.2019M651954)Natural Science Foundation of Jiangsu Province(Nos.BK20180204 and 20211552)Suzhou Key Medical Centre(No.Szzx201501)Gusu Health Personnel Training Project(No.GSWS2019030)Grants from Suzhou Government(No.SYS2019045).
文摘Monocarboxylic acid transporter 1(MCT1)maintains axonal function by transferring lactic acid from oligodendrocytes to axons.Subarachnoid hemorrhage(SAH)induces white matter injury,but the involvement of MCT1 is unclear.In this study,the SAH model of adult male Sprague-Dawley rats was used to explore the role of MCT1 in white matter injury after SAH.At 48 h after SAH,oligodendrocyte MCT1 was significantly reduced,and the exogenous overexpression of MCT1 significantly improved white matter integrity and long-term cognitive function.Motor training after SAH significantly increased the number of ITPR2+SOX10+oligodendrocytes and upregulated the level of MCT1,which was positively correlated with the behavioral ability of rats.In addition,miR-29b and miR-124 levels were significantly increased in SAH rats compared with non-SAH rats.Further intervention experiments showed that miR-29b and miR-124 could negatively regulate the level of MCT1.This study confirmed that the loss of MCT1 may be one of the mechanisms of white matter damage after SAH and may be caused by the negative regulation of miR-29b and miR-124.MCT1 may be involved in the neurological improvement of rehabilitation training after SAH.
