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. [Copyright &y& Elsevier]