Molecular analysis of Nogo expression in the hippocampus during development and following lesion and seizure.
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.
Meier
Susan
S
Institute of Anatomy, Department of Cell Biology and Neurobiology, Humboldt University Hospital (Charité), Oskar-Hertwig House, Philippstr. 12, Berlin, 10098 Germany.
Bräuer
Anja U
AU
Heimrich
Bernd
B
Schwab
Martin E
ME
Nitsch
Robert
R
Savaskan
Nicolai E
NE
D000818:Animals; D003714:Denervation; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D008959:Models, Neurological; D009185:Myelin Proteins / Q000096:biosynthesis* / Q000235:genetics; D009413:Nerve Fibers, Myelinated / Q000737:chemistry; D009474:Neurons / Q000737:chemistry; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D012640:Seizures / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D020033:Protein Isoforms; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C000603197:Rtn4 protein, rat; C486581:Rtn4r protein, rat