title: Role of CSPG receptor LAR phosphatase in restricting axon regeneration after CNS injury.
abstract: Extracellular matrix molecule chondroitin sulfate proteoglycans (CSPGs) are highly upregulated in scar tissues and form a potent chemical barrier for CNS axon regeneration. Recent studies support that the receptor protein tyrosine phosphatase σ (PTPσ) and its subfamily member leukocyte common antigen related phosphatase (LAR) act as transmembrane receptors to mediate CSPG inhibition. PTPσ deficiency increased regrowth of ascending axons into scar tissues and descending corticospinal tract (CST) axons into the caudal spinal cord after spinal cord injury (SCI). Pharmacological LAR inhibition enhanced serotonergic axon growth in SCI mice. However, transgenic LAR deletion on axon growth in vivo and the role of LAR in regulating regrowth of other fiber tracts have not been studied. Here, we studied the role of LAR in restricting regrowth of injured descending CNS axons in deficient mice. LAR deletion increased regrowth of serotonergic axons into scar tissues and caudal spinal cord after dorsal over-hemitransection. LAR deletion also stimulated regrowth of CST fibers into the caudal spinal cord. LAR protein was upregulated days to weeks after injury and co-localized to serotonergic and CST axons. Moreover, LAR deletion improved functional recovery by increasing BMS locomotor scores and stride length and reducing grid walk errors. This is the first transgenic study that demonstrates the crucial role of LAR in restricting regrowth of injured CNS axons.
authors.affiliation: Department of Neurosurgery, Affiliated Shanxi Dayi Hospital, Shanxi Academy of Medical Sciences, China; Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA; Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA; Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Dongsun
authors.initials: D
authors.lastname: Park
authors.affiliation: Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA; Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ohtake
authors.affiliation: Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA; Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA; Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Umar
authors.initials: U
authors.lastname: Hayat
authors.affiliation: Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA; Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Junjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA; Department of Neurology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Selzer
authors.affiliation: Department of Neurology and Neurological Science, Stanford University, Stanford, CA 94305, USA.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Longo
authors.affiliation: Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA; Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA. Electronic address: Shuxin.li@temple.edu.
authors.forename: Shuxin
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D001572:Benzofurans; D001710:Biotin / Q000031:analogs & derivatives; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003911:Dextrans; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D009154:Mutation / Q000235:genetics; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology*; D011712:Pyramidal Tracts / Q000378:metabolism / Q000473:pathology; D011804:Quinolines; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics / Q000378:metabolism*; D020127:Recovery of Function / Q000235:genetics / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors
chemical_list: C576715:(3aS,4S,9bS)-N-(2-(8-cyano-1-formyl-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo(3,2-c)quinolin-4-yl)-2-methylpropyl)-4,6-difluorobenzofuran-2-carboxyamide; D001572:Benzofurans; D003911:Dextrans; D011804:Quinolines; C076397:biotinylated dextran amine; D012701:Serotonin; D001710:Biotin; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2
keywords: Axon regeneration; CSPG receptor; Functional recovery; LAR phosphatase; Scar inhibition; Spinal cord injury