title: Involvement of brain-derived neurotrophic factor and sonic hedgehog in the spinal cord plasticity after neurotoxic partial removal of lumbar motoneurons.
abstract: Adult mammals could spontaneously achieve a partial sensory-motor recovery after spinal cord injury, by mechanisms including synaptic plasticity. We previously showed that this recovery is associated to the expression of synapsin-I, and that sonic hedgehog and Notch-1 could be also involved in plasticity. The role of brain-derived neurotrophic factor and glutamate receptors in regulating synaptic efficacy has been explored in the last decade but, although these mechanisms are now well-defined in the brain, the molecular mechanisms underlying the so called "spinal learning" are still less clear. Here, we measured the expression levels of choline acetyltransferase, synapsin-I, sonic hedgehog, Notch-1, glutamate receptor subunits (GluR1, GluR2, GluR4, NMDAR1) and brain-derived neurotrophic factor, in a motoneuron-depleted mouse spinal lesion model obtained by intramuscular injection of cholera toxin-B saporin. The lesion caused the down-regulation of the majority of analysed proteins. Moreover, we found that in lesioned but not in control spinal tissue, synapsin-I expression is associated to that of both brain-derived neurotrophic factor and sonic hedgehog, whereas GluR2 expression is linked to that of Shh. These results suggest that brain-derived neurotrophic factor and sonic hedgehog could collaborate in modulating synaptic plasticity after the removal of motoneurons, by a mechanism involving both pre- and post-synaptic processes. Interestingly, the involvement of sonic hedgehog showed here is novel, and offers new routes to address spinal cord plasticity and repair.
authors.affiliation: Department of Bio-Medical Sciences, Section of Physiology, University of Catania, Viale Andrea Doria 6, I95125 Catania, Italy. sarogulino@hotmail.com
authors.forename: Rosario
authors.initials: R
authors.lastname: Gulino
authors.forename: Massimo
authors.initials: M
authors.lastname: Gulisano
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D004195:Disease Models, Animal; D053823:Hedgehog Proteins / Q000502:physiology*; D008161:Lumbosacral Region / Q000502:physiology; D008297:Male; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D009473:Neuronal Plasticity / Q000502:physiology*; D009498:Neurotoxins / Q000633:toxicity*; D017729:Presynaptic Terminals / Q000473:pathology; D020127:Recovery of Function / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D055366:Synaptic Potentials / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D053823:Hedgehog Proteins; D009498:Neurotoxins; C465570:Shh protein, mouse