Cellular changes underlying hyperoxia-induced delay of white matter development.
Cellular changes underlying hyperoxia-induced delay of white matter development.
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高氧引起的白质发育延迟的细胞变化。
DOI：
10.1523/jneurosci.3942-10.2011
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发表时间：
2011-03-16
期刊：
影响因子：
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通讯作者：
Gallo V
中科院分区：
文献类型：
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作者：
Schmitz T;Ritter J;Mueller S;Felderhoff-Mueser U;Chew LJ;Gallo V
早产儿的神经发育受损经常由脑室周围白色物质损伤（PWMI）引起，这是一种与髓鞘形成异常相关的疾病。最近，据报道，暴露于高氧破坏髓鞘形成的新生大鼠。为了确定高氧诱导PWMI的原因，我们使用新生野生型、CNP-EGFP和GFAP-EGFP转基因小鼠从出生后第6天（P6）至出生后第8天（P8）暴露于80%氧气48小时，表征了白色物质（WM）中的细胞变化。髓鞘碱性蛋白（MBP）的表达和CC 1+少突胶质细胞在P8高氧后下降，但在P12和P15之间的恢复过程中恢复到对照水平。在P8，高氧导致NG 2 + O 4 −祖细胞凋亡，并减少NG 2+细胞增殖。其次是恢复NG 2+细胞群和增加少突胶质细胞在WM恢复后。尽管明显的细胞恢复，扩散张量成像（DTI）显示WM在P30和P60的缺陷。高氧不影响星形胶质细胞的存活和增殖，但改变了胶质细胞酸性蛋白（GFAP）和谷氨酸-天冬氨酸转运蛋白（GLAST）的表达。在P8和P12，WM组织中3 H-D-天冬氨酸摄取率也降低。此外，培养的星形胶质细胞暴露于高氧显示能力降低，以保护少突胶质细胞祖细胞（OPCs）对外源性谷氨酸的毒性作用。NBQX治疗可以预防这种效应。我们的分析揭示了谷氨酸稳态改变在高氧诱导的WM损伤中的作用。了解高氧诱导PWMI的细胞动力学和潜在机制将有助于未来的靶向治疗干预。
Impaired neurological development in premature infants frequently arises from periventricular white matter injury (PWMI), a condition associated with myelination abnormalities. Recently, exposure to hyperoxia was reported to disrupt myelin formation in neonatal rats. To identify the causes of hyperoxia-induced PWMI, we have characterized cellular changes in the white matter (WM) using neonatal wild-type, CNP-EGFP and GFAP-EGFP transgenic mice exposed to 48 hours of 80% oxygen from postnatal day 6 (P6) to postnatal day 8 (P8). Myelin basic protein (MBP) expression and CC1+ oligodendroglia decreased following hyperoxia at P8, but returned to control levels during recovery between P12 and P15. At P8, hyperoxia caused apoptosis of NG2+O4− progenitor cells and reduced NG2+ cell proliferation. This was followed by restoration of the NG2+ cell population and increased oligodendrogenesis in the WM after recovery. Despite apparent cellular recovery, diffusion tensor imaging (DTI) revealed WM deficiencies at P30 and P60. Hyperoxia did not affect survival or proliferation of astrocytes in vivo, but modified glial fibrillary acidic protein (GFAP) and glutamate-aspartate transporter (GLAST) expression. The rate of 3H-D-aspartic acid uptake in WM tissue was also decreased at P8 and P12. Furthermore, cultured astrocytes exposed to hyperoxia showed a reduced capacity to protect oligodendrocyte progenitor cells (OPCs) against the toxic effects of exogenous glutamate. This effect was prevented by NBQX treatment. Our analysis reveals a role for altered glutamate homeostasis in hyperoxia-induced WM damage. Understanding the cellular dynamics and underlying mechanisms involved in hyperoxia-induced PWMI will allow for future targeted therapeutic intervention.