title: Regulation of Nogo and Nogo receptor during the development of the entorhino-hippocampal pathway and after adult hippocampal lesions.
abstract: Axonal regeneration in the adult CNS is limited by the presence of several inhibitory proteins associated with myelin. Nogo-A, a myelin-associated inhibitor, is responsible for axonal outgrowth inhibition in vivo and in vitro. Here we study the onset and maturation of Nogo-A and Nogo receptor in the entorhino-hippocampal formation of developing and adult mice. We also provide evidence that Nogo-A does not inhibit embryonic hippocampal neurons, in contrast to other cell types such as cerebellar granule cells. Our results also show that Nogo and Nogo receptor mRNA are expressed in the adult by both principal and local-circuit hippocampal neurons, and that after lesion, Nogo-A is also transiently expressed by a subset of reactive astrocytes. Furthermore, we analyzed their regulation after kainic acid (KA) treatment and in response to the transection of the entorhino-hippocampal connection. We found that Nogo-A and Nogo receptor are differentially regulated after kainic acid or perforant pathway lesions. Lastly, we show that the regenerative potential of lesioned entorhino-hippocampal organotypic slice co-cultures is increased after blockage of Nogo-A with two IN-1 blocking antibodies. In conclusion, our results show that Nogo and its receptor might play key roles during development of hippocampal connections and that they are implicated in neuronal plasticity in the adult.
authors.affiliation: Development and Regeneration of the CNS, Barcelona Science Park-IRBB, University of Barcelona, E-08028 Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Mingorance
authors.forename: Xavier
authors.initials: X
authors.lastname: Fontana
authors.forename: Marta
authors.initials: M
authors.lastname: Solé
authors.forename: Ferran
authors.initials: F
authors.lastname: Burgaya
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Ureña
authors.forename: Felicia Y H
authors.initials: FY
authors.lastname: Teng
authors.forename: Bor Luen
authors.initials: BL
authors.lastname: Tang
authors.forename: David
authors.initials: D
authors.lastname: Hunt
authors.forename: Patrick N
authors.initials: PN
authors.lastname: Anderson
authors.forename: John R
authors.initials: JR
authors.lastname: Bethea
authors.forename: Martin E
authors.initials: ME
authors.lastname: Schwab
authors.forename: Eduardo
authors.initials: E
authors.lastname: Soriano
authors.forename: José A
authors.initials: JA
authors.lastname: del Río
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001930:Brain Injuries / Q000139:chemically induced / Q000503:physiopathology; D019556:COS Cells; D018728:Entorhinal Cortex / Q000196:embryology / Q000293:injuries / Q000502:physiology*; D005333:Fetus; D058851:GPI-Linked Proteins; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005911:Gliosis / Q000378:metabolism / Q000503:physiopathology; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D006624:Hippocampus / Q000196:embryology / Q000293:injuries / Q000502:physiology*; D007608:Kainic Acid; D051379:Mice; D009185:Myelin Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D019580:Perforant Pathway / Q000196:embryology / Q000293:injuries / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism
chemical_list: D000906:Antibodies; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat; C419790:Rtn4r protein, mouse; C486581:Rtn4r protein, rat; D007608:Kainic Acid