Structural plasticity of the adult CNS. Negative control by neurite growth inhibitory signals |
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| Institution: | 1. Department of Ophthalmology, University of Rochester, Rochester, NY 14620, USA;2. Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620, USA;3. Department of Pathology and Laboratory Medicine, University of Rochester, Rochester, NY 14620, USA;4. Department of Biomedical Engineering, Robert B. Goergen Hall, University of Rochester, Rochester, NY 14627, USA;5. Department of Orthopedics and Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA;6. Center for Oral Biology, University of Rochester, Rochester, NY 14642, USA;7. Department of Environmental Medicine, University of Rochester, Rochester, NY 14642 USA;8. Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA;9. Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53715, USA;10. NSF Center for Sustainable Nanotechnology, Department of Chemistry, University of Wisconsin, Madison, WI 53706, USA;11. Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53715, USA;12. Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI 53715, USA;13. Department of Ophthalmic Research, Cole Eye Institute and Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA;14. Center for Visual Science, University of Rochester, Rochester, NY 14620, USA;15. UR Stem Cell and Regenerative Medicine Center, Rochester, NY 14620, USA;16. Materials Science Program, University of Rochester, Rochester, NY 14620, USA;17. Department of Chemical Engineering, University of Rochester, NY 14620, USA;1. Department of Food Science and Technology, Oregon State University, Corvallis 97330;2. Protein Research Center, Agropur, Le Sueur, MN 56058;1. Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet, Hyderabad 500078, India;2. Dr Reddy’s Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500046, India;1. Department of Pediatric Orthopaedics Surgery, University hospital of Montpellier, 34295 Montpellier, France;2. Department of Histopathology, University hospital of Montpellier, 34295 Montpellier, France;3. Department of Pediatric Radiology, University hospital of Montpellier, 34295 Montpellier, France;4. Department of Pediatric Orthopedics Surgery, University hospital of Beirut, Beirut, Lebanon;5. Department of Pediatric Surgery, University hospital of Clermont-Ferrand, 69003 Clermont-Ferrand, France |
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| Abstract: | The neuronal network of the adult central nervous system (CNS) retains a limited capacity for growth and structural change. This structural plasticity has been best studied in the context of lesion-induced growth and repair. More recently, structural changes underlying functional plasticity occurring under specific physiological conditions have also been documented, in particular in the cortex and the hippocampus. Areas known for their adult plastic potential retain high levels of the growth associated protein GAP-43, suggesting a persistence of important components of the intracellular growth machinery throughout life. Interestingly, a pronounced negative correlation exists between the levels of GAP-43 and myelination in the adult CNS. Because CNS myelin contains potent neurite growth inhibitory membrane proteins, neurite growth, sprouting and plasticity were investigated in the spinal cord and brain in areas where oligodendrocyte development and myelin formation was experimentally prevented, or in the presence of an inhibitor neutralizing antibody (mAB-IN-1). In all areas, lesion-induced or spontaneous sprouting was enhanced, in parallel with persistent high levels of GAP-43. Thus, spontaneous sprouting of side branches occurred from retinal axons in the optic nerve in the absence of myelin, and target-deprived retinal axons showed increased sprouting and innervation of the contralateral optic tectum in the presence of mAB IN-1. In experimentally myelin-free spinal cords collaterals from intact dorsal roots grew over long distances to innervate deafferented target regions following the section of three dorsal roots. Similarly, the corticospinal tract sprouted across the the midline and re-established a dense plexus of fibres on the contralateral side of the spinal cord following section of one corticospinal tract in juvenile rats. Following bilateral dorsal hemisection of the spinal cord including both corticospinal tracts in young and adult rats, long distance regeneration of corticospinal fibres leading to significant functional improvements of locomotion and certain reflexes was induced by the neurite growth inhibitor neutralizing antibody IN-1. |
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