title: Mice lacking L1 cell adhesion molecule have deficits in locomotion and exhibit enhanced corticospinal tract sprouting following mild contusion injury to the spinal cord.
abstract: L1 is a member of the immunoglobulin superfamily of cell adhesion molecules that is associated with axonal growth, including formation of the corticospinal tract (CST). The present study describes the effects of L1 deletion on hindlimb function in locomotion, and examines the role of L1 in recovery and remodeling after contusive spinal cord injury (SCI) in mice. Uninjured adult L1 knockout (Y/-) mice had impaired performance on locomotor tests compared with their wild-type littermates (Y/+). Anterograde tracing demonstrated that CST axons project to thoracic, but not lumbar, levels of the spinal cord of Y/- mice, and revealed a diversion of these fibers from their position in the base of the dorsal columns. Retrograde tracing also revealed reduced numbers of descending projections from paraventricular hypothalamus and red nuclei to the lumbar spinal cord in Y/- mice. SCI at the mid-thoracic level produced a lesion encompassing the center of the spinal cord, including the site of the dorsal CST and surrounding gray matter (GM). The injury caused lasting deficits in fine aspects of locomotion. There was no effect of genotype on final lesion size or the growth of axons into the lesion area. However, injured Y/- mice demonstrated a robust expansion of CST projections throughout the GM of the cervical and thoracic spinal cord rostral to the lesion compared with Y/+ littermates. Thus, L1 is important for the development of multiple spinal projections and also contributes to the restriction of CST sprouting rostral to the site of a SCI in adults.
authors.affiliation: Spinal Trauma and Repair Laboratories, Department of Physiology & Cell Biology, The Ohio State University College of Medicine and Public Health, Columbus, OH 43210, USA. jakeman.1@osu.edu
authors.forename: Lyn B
authors.initials: LB
authors.lastname: Jakeman
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Kurt M
authors.initials: KM
authors.lastname: Lucin
authors.forename: Dana M
authors.initials: DM
authors.lastname: McTigue
mesh_terms: D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002452:Cell Count / Q000379:methods; D003911:Dextrans; D005260:Female; D007839:Functional Laterality / Q000235:genetics; D006614:Hindlimb / Q000503:physiopathology; D007150:Immunohistochemistry / Q000379:methods; D008124:Locomotion / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009416:Nerve Regeneration; D039842:Neural Cell Adhesion Molecule L1 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D011597:Psychomotor Performance / Q000502:physiology; D011712:Pyramidal Tracts / Q000473:pathology / Q000503:physiopathology*; D020127:Recovery of Function / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013119:Spinal Cord Injuries / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D013266:Stilbamidines; D013997:Time Factors
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D003911:Dextrans; D039842:Neural Cell Adhesion Molecule L1; D013266:Stilbamidines; C076397:biotinylated dextran amine; D001710:Biotin