title: Enhanced regeneration and functional recovery after spinal root avulsion by manipulation of the proteoglycan receptor PTPσ.
abstract: Following root avulsion, spinal nerves are physically disconnected from the spinal cord. Severe motoneuron death and inefficient axon regeneration often result in devastating motor dysfunction. Newly formed axons need to extend through inhibitory scar tissue at the CNS-PNS transitional zone before entering into a pro-regenerative peripheral nerve trajectory. CSPGs are dominant suppressors in scar tissue and exert inhibition via neuronal receptors including PTPσ. Previously, a small peptide memetic of the PTPσ wedge region named ISP (Intracellular Sigma Peptide) was generated, and its capabilities to target PTPσ and relieve CSPG inhibition were validated. Here, we demonstrate that after ventral root avulsion and immediate re-implantation, modulation of PTPσ by systemic delivery of ISP remarkably enhanced regeneration. ISP treatment reduced motoneuron death, increased the number of axons regenerating across scar tissue, rebuilt healthy neuromuscular junctions and enhanced motor functional recovery. Our study shows that modulation of PTPσ is a potential therapeutic strategy for root avulsion.
authors.affiliation: School of Biomedical Sciences, Division of Anatomy, the University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.affiliation: School of Biomedical Sciences, Division of Anatomy, the University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.
authors.forename: Connie
authors.initials: C
authors.lastname: Wong
authors.affiliation: School of Biomedical Sciences, Division of Anatomy, the University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Biomedical Sciences, Division of Anatomy, the University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.
authors.forename: Carolin
authors.initials: C
authors.lastname: Ruven
authors.affiliation: School of Biomedical Sciences, Division of Anatomy, the University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.
authors.forename: Liumin
authors.initials: L
authors.lastname: He
authors.affiliation: School of Biomedical Sciences, Division of Anatomy, the University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Neurosciences, Case Western Reserve University School of Medicine, 2109 Adelbert Road Cleveland, OH 44106, USA.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Lang
authors.affiliation: Department of Neurosciences, Case Western Reserve University School of Medicine, 2109 Adelbert Road Cleveland, OH 44106, USA.
authors.forename: Jerry
authors.initials: J
authors.lastname: Silver
authors.affiliation: School of Biomedical Sciences, Division of Anatomy, the University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.|State Key Laboratory of Brain and Cognitive Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.|GHM Institute of CNS Regeneration, Jinan University, Guangzhou, China.
authors.forename: Wutian
authors.initials: W
authors.lastname: Wu
mesh_terms: D000818:Animals; D002491:Central Nervous System Agents / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D011509:Proteoglycans / Q000378:metabolism; D011843:Radiculopathy / Q000503:physiopathology* / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000378:metabolism*; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D058630:Spinal Cord Regeneration / Q000187:drug effects / Q000502:physiology*; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D002491:Central Nervous System Agents; D047908:Intracellular Signaling Peptides and Proteins; D011509:Proteoglycans; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2