title: Myelin does not influence the choice behaviour of entorhinal axons but strongly inhibits their outgrowth length in vitro.
abstract: Myelin is crucial for the stabilization of the entorhinohippocampal projection during late development and is a non-permissive substrate for regrowing axons after lesion in the adult brain. We used two in vitro assays to analyse the impact of myelin on rat entorhinohippocampal projection neurons. A stripe assay was used to study the impact of myelin on the choice behaviour of axons from the entorhinal cortex (EC). Given a choice between alternating hippocampal membrane lanes from developmental stages ranging from early postnatal to adult, EC axons preferred to extend on early postnatal hippocampal membranes. Neither the neutralization of myelin-associated factors by a specific antibody (IN-1) nor the separation of myelin from membranes interfered with the axons' choice behaviour. The entorhinal axons showed no preference in the membrane combination of adult and myelin-free adult hippocampal membranes. These stripe assay experiments demonstrate that support for EC axon choice in the developing hippocampus is maturation-dependent and is not influenced by myelin. The application of IN-1 in the outgrowth assay and the separation of myelin from membranes, enhanced elongation of outgrowing entorhinal axons on adult hippocampal membranes, whereas a control antibody did not. This shows that myelin-associated factors have a strong inhibitory effect on the outgrowth length of entorhinal axons. In conclusion, we suggest that axonal elongation in the entorhinohippocampal system during development is strongly influenced by myelin-associated growth inhibition factors and that specific target finding of entorhinal axons is regulated by a different mechanism.
authors.affiliation: Department of Cell- and Neurobiology, Humboldt University Hospital, Charité, Berlin, Germany.
authors.forename: N E
authors.initials: NE
authors.lastname: Savaskan
authors.forename: M
authors.initials: M
authors.lastname: Plaschke
authors.forename: O
authors.initials: O
authors.lastname: Ninnemann
authors.forename: A A
authors.initials: AA
authors.lastname: Spillmann
authors.forename: M E
authors.initials: ME
authors.lastname: Schwab
authors.forename: R
authors.initials: R
authors.lastname: Nitsch
authors.forename: T
authors.initials: T
authors.lastname: Skutella
mesh_terms: D000367:Age Factors; D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D018728:Entorhinal Cortex / Q000166:cytology*; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000235:genetics; D004676:Myelin Basic Protein / Q000032:analysis; D009186:Myelin Sheath / Q000737:chemistry / Q000502:physiology*; D018992:Myelin-Associated Glycoprotein / Q000032:analysis; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D019006:Neural Cell Adhesion Molecules / Q000235:genetics; D016501:Neurites / Q000502:physiology; D009836:Oligodendroglia / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar