title: Antisense Morpholino Oligonucleotides Reduce Neurofilament Synthesis and Inhibit Axon Regeneration in Lamprey Reticulospinal Neurons.
abstract: The sea lamprey has been used as a model for the study of axonal regeneration after spinal cord injury. Previous studies have suggested that, unlike developing axons in mammal, the tips of regenerating axons in lamprey spinal cord are simple in shape, packed with neurofilaments (NFs), and contain very little F-actin. Thus it has been proposed that regeneration of axons in the central nervous system of mature vertebrates is not based on the canonical actin-dependent pulling mechanism of growth cones, but involves an internal protrusive force, perhaps generated by the transport or assembly of NFs in the distal axon. In order to assess this hypothesis, expression of NFs was manipulated by antisense morpholino oligonucleotides (MO). A standard, company-supplied MO was used as control. Axon retraction and regeneration were assessed at 2, 4 and 9 weeks after MOs were applied to a spinal cord transection (TX) site. Antisense MO inhibited NF180 expression compared to control MO. The effect of inhibiting NF expression on axon retraction and regeneration was studied by measuring the distance of axon tips from the TX site at 2 and 4 weeks post-TX, and counting the number of reticulospinal neurons (RNs) retrogradely labeled by fluorescently-tagged dextran injected caudal to the injury at 9 weeks post-TX. There was no statistically significant effect of MO on axon retraction at 2 weeks post-TX. However, at both 4 and 9 weeks post-TX, inhibition of NF expression inhibited axon regeneration.
authors.affiliation: Shriners Hospital Pediatric Research Center (Center for Neural Repair and Rehabilitation), 3500 North Broad Street, Philadelphia, United States of America.
authors.forename: Guixin
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Shriners Hospital Pediatric Research Center (Center for Neural Repair and Rehabilitation), 3500 North Broad Street, Philadelphia, United States of America.
authors.forename: Li-qing
authors.initials: LQ
authors.lastname: Jin
authors.affiliation: Shriners Hospital Pediatric Research Center (Center for Neural Repair and Rehabilitation), 3500 North Broad Street, Philadelphia, United States of America.
authors.forename: Jianli
authors.initials: J
authors.lastname: Hu
authors.affiliation: Shriners Hospital Pediatric Research Center (Center for Neural Repair and Rehabilitation), 3500 North Broad Street, Philadelphia, United States of America.
authors.forename: William
authors.initials: W
authors.lastname: Rodemer
authors.affiliation: Shriners Hospital Pediatric Research Center (Center for Neural Repair and Rehabilitation), 3500 North Broad Street, Philadelphia, United States of America; Department of Neurology, Temple University School of Medicine, 3500 North Broad Street, Philadelphia, United States of America.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Selzer
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D029941:Fish Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D007382:Intermediate Filaments / Q000378:metabolism* / Q000502:physiology; D007798:Lampreys / Q000378:metabolism / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D016900:Neurofilament Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D061848:Optical Imaging; D013116:Spinal Cord / Q000378:metabolism / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology
chemical_list: D029941:Fish Proteins; D016900:Neurofilament Proteins; D016376:Oligonucleotides, Antisense