title: Tenascin-R restricts posttraumatic remodeling of motoneuron innervation and functional recovery after spinal cord injury in adult mice.
abstract: Tenascin-R (TNR) is an extracellular glycoprotein in the CNS implicated in neural development and plasticity. Its repellent properties for growing axons in a choice situation with a conducive substrate in vitro have indicated that TNR may impede regeneration in the adult mammalian CNS. Here we tested whether constitutive lack of TNR has beneficial impacts on recovery from spinal cord injury in adult mice. Using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale, we found that open-field locomotion in TNR-deficient (TNR-/-) mice recovered better that in wild-type (TNR+/+) littermates after compression of the thoracic spinal cord. We also designed, validated, and applied a motion analysis approach allowing numerical assessment of motor functions. We found, in agreement with the BBB score, that functions requiring low levels of supraspinal control such as plantar stepping improved more in TNR-/- mice. This was not the case for motor tasks demanding precision such as ladder climbing. Morphological analyses revealed no evidence that improved recovery of some functions in the mutant mice were attributable to enhanced tissue sparing or axonal regrowth. Estimates of perisomatic puncta revealed reduced innervation by cholinergic and GABAergic terminals around motoneurons in intact TNR-/- compared with TNR+/+ mice. Relative to nonlesioned animals, spinal cord repair was associated with increase in GABAergic and decrease of glutamatergic puncta in TNR-/- but not in TNR+/+ mice. Our results suggest that TNR restricts functional recovery by limiting posttraumatic remodeling of synapses around motoneuronal cell bodies where TNR is normally expressed in perineuronal nets.
authors.affiliation: Zentrum für Molekulare Neurobiologie, Universität Hamburg, D-20246 Hamburg, Germany.
authors.forename: Ivayla
authors.initials: I
authors.lastname: Apostolova
authors.forename: Andrey
authors.initials: A
authors.lastname: Irintchev
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology*; D009416:Nerve Regeneration; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology*; D019063:Tenascin / Q000378:metabolism*
chemical_list: D019063:Tenascin; C074638:tenascin R