title: Antagonizing Nogo-receptor 1 promotes the number of cultured dopaminergic neurons and elongates their neurites.
abstract: The myelin-associated protein Nogo-A and its receptor Nogo-receptor 1 (NgR1) are known as potent growth inhibitors of the adult central nervous system (CNS). Nogo-A is mostly expressed on the surface of oligodendrocytes, but is also found in neurons of the adult and developing CNS. This observation suggests that Nogo-A serves additional functions in the brain. Hence, in the present study, we investigated the effects of antagonizing NgR1 on cultured organotypic and dissociated dopaminergic neurons. For that purpose ventral mesencephalic cultures from E14 rat embryos were grown in absence or presence of the NgR1 antagonist NEP1-40 for 1 week. Treatment with NEP1-40 significantly increased cell densities of tyrosine hydroxylase-immunoreactive neurons. Moreover, organotypic ventral mesencephalic cultures displayed a significantly bigger volume after NEP1-40 treatment. Morphological analysis of tyrosine hydroxylase-positive neurons disclosed longer neurites and higher numbers of primary neurites in dissociated cultures incubated with NEP1-40, whereas soma size was not changed. In conclusion, our findings demonstrate that interfering with Nogo-A signaling by antagonizing NgR1 modulates dopaminergic neuron properties during development. These observations highlight novel aspects of the role of Nogo-A in the CNS and might have an impact in the context of Parkinson's disease.
authors.affiliation: aDepartment of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster bGraduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Seiler
authors.forename: Dario
authors.initials: D
authors.lastname: Pollini
authors.forename: Stefano
authors.initials: S
authors.lastname: Di Santo
authors.forename: Hans R
authors.initials: HR
authors.lastname: Widmer
mesh_terms: D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005333:Fetus; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009185:Myelin Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D000070816:Nogo Receptor 1; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D058851:GPI-Linked Proteins; D009185:Myelin Proteins; C457761:NEPI-40 protein, rat; D000070816:Nogo Receptor 1; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C486581:Rtn4r protein, rat