title: Entrapment via synaptic-like connections between NG2 proteoglycan+ cells and dystrophic axons in the lesion plays a role in regeneration failure after spinal cord injury.
abstract: NG2 is purportedly one of the most growth-inhibitory chondroitin sulfate proteoglycans (CSPGs) produced after spinal cord injury. Nonetheless, once the severed axon tips dieback from the lesion core into the penumbra they closely associate with NG2+ cells. We asked if proteoglycans play a role in this tight cell-cell interaction and whether overadhesion upon these cells might participate in regeneration failure in rodents. Studies using varying ratios of CSPGs and adhesion molecules along with chondroitinase ABC, as well as purified adult cord-derived NG2 glia, demonstrate that CSPGs are involved in entrapping neurons. Once dystrophic axons become stabilized upon NG2+ cells, they form synaptic-like connections both in vitro and in vivo. In NG2 knock-out mice, sensory axons in the dorsal columns dieback further than their control counterparts. When axons are double conditioned to enhance their growth potential, some traverse the lesion core and express reduced amounts of synaptic proteins. Our studies suggest that proteoglycan-mediated entrapment upon NG2+ cells is an additional obstacle to CNS axon regeneration.
authors.affiliation: Case Western Reserve University, Department of Neurosciences, Cleveland, Ohio 44106.
authors.forename: Angela R
authors.initials: AR
authors.lastname: Filous
authors.affiliation: Case Western Reserve University, Department of Neurosciences, Cleveland, Ohio 44106.
authors.forename: Amanda
authors.initials: A
authors.lastname: Tran
authors.affiliation: Case Western Reserve University, Department of Neurosciences, Cleveland, Ohio 44106.
authors.forename: C James
authors.initials: CJ
authors.lastname: Howell
authors.affiliation: Case Western Reserve University, Department of Neurosciences, Cleveland, Ohio 44106.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Busch
authors.affiliation: Case Western Reserve University, Department of Neurosciences, Cleveland, Ohio 44106.
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Evans
authors.affiliation: Tumor Microenvironment Program, Cancer Center, Sanford-Burnham Medical Research Institute, La Jolla, California 92037.
authors.forename: William B
authors.initials: WB
authors.lastname: Stallcup
authors.affiliation: The Johns Hopkins School of Medicine, The Solomon H. Snyder Department of Neuroscience, Baltimore, Maryland 21205, and.
authors.forename: Shin H
authors.initials: SH
authors.lastname: Kang
authors.affiliation: The Johns Hopkins School of Medicine, The Solomon H. Snyder Department of Neuroscience, Baltimore, Maryland 21205, and.
authors.forename: Dwight E
authors.identifier: http://orcid.org/0000-0002-7133-7378
authors.initials: DE
authors.lastname: Bergles
authors.affiliation: Department of Neurobiology and Behavior, SUNY at Stony Brook, Stony Brook, New York 11794-5230.
authors.forename: Seong-il
authors.initials: SI
authors.lastname: Lee
authors.affiliation: Department of Neurobiology and Behavior, SUNY at Stony Brook, Stony Brook, New York 11794-5230.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Levine
authors.affiliation: Case Western Reserve University, Department of Neurosciences, Cleveland, Ohio 44106, jxs10@cwru.edu.
authors.forename: Jerry
authors.identifier: http://orcid.org/0000-0001-5002-2599
authors.initials: J
authors.lastname: Silver
mesh_terms: D000818:Animals; D000941:Antigens / Q000235:genetics / Q000502:physiology*; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D002450:Cell Communication / Q000502:physiology*; D058948:Cell Tracking; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000502:physiology; D005353:Fibronectins / Q000502:physiology; D005727:Ganglia, Spinal / Q000503:physiopathology / Q000648:ultrastructure; D019012:Integrin beta1 / Q000502:physiology; D007797:Laminin / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000503:physiopathology; D009416:Nerve Regeneration / Q000502:physiology*; D011509:Proteoglycans / Q000235:genetics / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology*; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D011508:Chondroitin Sulfate Proteoglycans; D005353:Fibronectins; D019012:Integrin beta1; D007797:Laminin; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4
keywords: NG2 proteoglycan; chondroitinase; dystrophic axons; glial scar; oligodendrocyte progenitor cells; spinal cord injury