The glutamate transporter EAAT2 is transiently expressed in developing human cerebral white matter
The glutamate transporter EAAT2 is transiently expressed in developing human cerebral white matter
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DOI：
10.1002/cne.21289
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发表时间：
2007-04-20
影响因子：
2.5
通讯作者：
Rosenberg, Paul A.
中科院分区：
文献类型：
--
作者：
Desilva, Tara M.;Kinney, Hannah C.;Rosenberg, Paul A.
早产儿脑性瘫痪的主要脑部异常是脑室周围白质软化（PVL），一种未成熟的大脑白色物质的病变。少突胶质细胞前体（前OL; 04（+）01（-））在PVL的高峰时间范围（24-32孕周）期间在人脑白色物质中占主导地位，并且易受兴奋性毒性的影响。我们假设PVL部分反映了脑缺血/再灌注对前OL的兴奋性毒性。在能量衰竭的情况下谷氨酸转运的抑制是细胞外谷氨酸病理性积累的主要来源。在这里，我们确定和本地化的谷氨酸转运蛋白在人大脑白色物质的年龄范围内的PV-L。用地高辛标记的探针直接对EAAT 1、EAAT 2和EAAT 3的全长编码区进行原位杂交。EAAT 2 mRNA在PVL发病高峰期在人胎儿白色物质中丰富，到出生后2个月几乎消失。它的发育模式与EAAT 1和EAAT 3 mRNA的发育模式差异显著。免疫印迹表明，EAAT 2蛋白在早期发展相对于成人的价值是高度表达。双标记免疫细胞化学检测到EAAT 2在OLs中，但不是在人胎儿白色物质中的星形胶质细胞或轴突中。我们得出结论，EAAT 2的瞬时表达发生在PVL的峰值脆弱性的窗口，这表明这种发展上调转运蛋白可能是一个主要来源的细胞外谷氨酸在缺血性损伤的早产儿脑白色问题。
The major brain abnormality underlying cerebral palsy in premature infants is periventricular leukomalacia (PVL), a lesion of the immature cerebral white matter. Oligodendrocyte precursors (pre-OLs; 04(+)01(-)) predominate in human cerebral white matter during the peak time frame for PVL (24-32 gestational weeks) and are vulnerable to excitotoxicity. We hypothesize that PVL reflects, in part, excitotoxicity to pre-OLs resulting from cerebral ischemia/reperfusion. Reversal of glutamate transport in the setting of energy failure is a major source of pathologic accumulation of extracellular glutamate. Here, we identify and localize the glutamate transporters in human cerebral white matter during the age range of PV-L. In situ hybridization was performed with digoxigenin-labeled probes directed against the full-length coding regions of EAAT1, EAAT2, and EAAT3. EAAT2 mRNA was abundant in human fetal white matter during the period of peak incidence of PVL and virtually disappeared by 2 postnatal months. Its developmental profile differed significantly from that of both EAAT1 and EAAT3 mRNA. Immunoblotting demonstrated that EAAT2 protein was highly expressed in early development relative to adult values. Double-label immunocytochemistry detected EAAT2 in OLs but not astrocytes or axons in the human fetal white matter. We conclude that transient expression of EAAT2 occurs during the window of peak vulnerability for PVL, suggesting that this developmentally up-regulated transporter may be a major source of extracellular glutamate in ischemic injury to the cerebral white matter of the preterm infant.