Molecular analysis of Nogo expression in the hippocampus during development and following lesion and seizure (Retracted article. See vol. 25, pg. 2853, 2011)
Molecular analysis of Nogo expression in the hippocampus during development and following lesion and seizure (Retracted article. See vol. 25, pg. 2853, 2011)
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DOI：
10.1096/fj.02-0453fje
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发表时间：
2003-04-01
期刊：
影响因子：
4.8
通讯作者：
Savaskan, NE
中科院分区：
文献类型：
--
作者：
Meier, S;Bräuer, AU;Savaskan, NE
Nogo基因编码一种完整的膜蛋白，主要负责髓磷脂的神经突抑制特性。在此，我们分析了Nogo-A、Nogo-B、Nogo-C和Nogo-66受体（Ng66R） mRNA在海马发育和损伤诱导的轴突发芽过程中的表达模式。除齿状颗粒细胞外，Nogo-A、Nogo-B和Ng66R转录本先于髓鞘形成，并在出生后0天（P0）在所有主要海马细胞层中高表达。在海马主要细胞层的P0处仅发现少量Nogo-C表达。成年后，所有的Nogo剪接变异体及其受体都在海马的神经元细胞层中表达，这与髓鞘碱性蛋白mRNA的表达模式相反，髓鞘碱性蛋白mRNA的表达模式揭示了除少突胶质细胞外Nogo基因表达的神经元来源。海马去神经支配后，Nogo基因表现出同型特异性的时间调控。所有的Nogo基因都在海马细胞层中受到强烈调节，而Ng66R转录本在对侧皮层中显著增加。这些数据可以在蛋白质水平上得到证实。此外，kainate诱导癫痫发作后Nogo-A表达上调。我们的数据显示，神经元在发育过程中以一种明显可区分的模式表达Nogo基因。在结构重排的早期阶段，这种表达在损伤后进一步动态和特异性地改变。因此，我们的研究结果表明Nogo-A， -B和-C在海马重组的发育和稳定阶段发挥作用。综合这些数据，高可塑性大脑区域的神经元表达Nogo基因的发现支持了Nogo可能在形成神经元回路中发挥其已知的神经元生长抑制活性之外的功能的假设。
The Nogo gene encodes an integral membrane protein mainly responsible for the neurite inhibition properties of myelin. Here, we analyzed the expression pattern of Nogo-A, Nogo-B, and Nogo-C and Nogo-66 receptor (Ng66R) mRNA during hippocampal development and lesion-induced axonal sprouting. Nogo-A and Nogo-B and Ng66R transcripts preceded the progress of myelination and were highly expressed at postnatal day zero (P0) in all principal hippocampal cell layers, with the exception of dentate granule cells. Only a slight Nogo-C expression was found at P0 in the principal cell layers of the hippocampus. During adulthood, all Nogo splice variants and their receptor were expressed in the neuronal cell layers of the hippocampus, in contrast to the myelin basic protein mRNA expression pattern, which revealed a neuronal source of Nogo gene expression in addition to oligodendrocytes. After hippocampal denervation, the Nogo genes showed an isoform-specific temporal regulation. All Nogo genes were strongly regulated in the hippocampal cell layers, whereas the Ng66R transcripts showed a significant increase in the contralateral cortex. These data could be confirmed on protein levels. Furthermore, Nogo-A expression was up-regulated after kainate-induced seizures. Our data show that neurons express Nogo genes with a clearly distinguishable pattern during development. This expression is further dynamically and isoform-specifically altered after lesioning during the early phase of structural rearrengements. Thus, our results indicate a role for Nogo-A, -B, and -C during development and during the stabilization phase of hippocampal reorganization. Taken together with these data, the finding that neurons in a highly plastic brain region express Nogo genes supports the hypothesis that Nogo may function beyond its known neuronal growth inhibition activity in shaping neuronal circuits.