Meier Susan, Bräuer Anja U, Heimrich Bernd, Schwab Martin E, Nitsch Robert, Savaskan Nicolai E
Institute of Anatomy, Department of Cell Biology and Neurobiology, Humboldt University Hospital (Charité), Oskar-Hertwig House, Philippstr. 12, Berlin, 10098 Germany.
FASEB J. 2003 Jun;17(9):1153-5. doi: 10.1096/fj.02-0453fje. Epub 2003 Apr 8.
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.
Nogo基因编码一种主要负责髓磷脂神经突抑制特性的整合膜蛋白。在此，我们分析了海马体发育和损伤诱导的轴突发芽过程中Nogo-A、Nogo-B、Nogo-C和Nogo-66受体（Ng66R）mRNA的表达模式。Nogo-A、Nogo-B和Ng66R转录本先于髓鞘形成过程出现，并在出生后第0天（P0）在海马体所有主要细胞层中高表达，但齿状颗粒细胞除外。在P0时，仅在海马体主要细胞层中发现轻微的Nogo-C表达。成年期，与髓鞘碱性蛋白mRNA表达模式不同，所有Nogo剪接变体及其受体均在海马体的神经元细胞层中表达，这表明除少突胶质细胞外，神经元也是Nogo基因的表达来源。海马体去神经支配后，Nogo基因呈现出异构体特异性的时间调控。所有Nogo基因在海马体细胞层中受到强烈调控，而Ng66R转录本在对侧皮质中显著增加。这些数据在蛋白质水平上也得到了证实。此外，在海藻酸诱导的癫痫发作后，Nogo-A表达上调。我们的数据表明，神经元在发育过程中以明显可区分的模式表达Nogo基因。在结构重排的早期阶段损伤后，这种表达会进一步动态且异构体特异性地改变。因此，我们的结果表明Nogo-A、-B和-C在海马体重组的发育和稳定阶段发挥作用。结合这些数据，在一个高度可塑性脑区的神经元表达Nogo基因这一发现支持了这样一种假说，即Nogo在塑造神经元回路方面可能具有超出其已知的神经元生长抑制活性的功能。
