Gulino R, Gulisano M (2008) Sonic hedgehog expression and glial reaction after neurotoxic lesion of adult mice spinal cord by Cholera Toxin-B Saporin. Neuroscience 2008 Abstracts 124.14/B14. Society for Neuroscience, Washington, DC.
Summary: The spinal cord (SC) has ever been considered non-neurogenic because no neurons seem to be generated in the intact SC and only very few recent articles have reported spontaneous generation of new neurons after lesion. Conversely, many studies have demonstrated the occurrence of glial reaction after either mechanical or selective neurotoxic lesion. Sonic hedgehog (Shh) is a member of hedgehog family of secreted glycoproteins, which stimulate cell proliferation as well as neuron and oligodendrocyte differentiation during either development and adulthood. Few data are available about its role in the adult SC after injury. In this study, we used Cholera toxin-B saporin (CTB-sap), a retrogradely transported, ribosome-inactivating toxin, to induce a mild neurotoxic depletion of motoneurons within lumbar SC and to subsequently study the expression levels of Shh and the possible cell proliferation and differentiation within the depleted SC of young adult mice. After an injection of CTB-sap into the gastrocnemius muscle, we found a 30% depletion of lumbar SC motoneurons, and a comparable decrease of ChAT expression levels in the lumbar SC, one week after lesion. Moreover, we found a significant down-regulation of Shh expression, which significantly correlate with ChAT decrease. Both proteins recovered to near normal levels of expression at one month after lesion. The expression of ChAT also correlate with the performance of mice on a grid walk test. So, the observed spontaneous recovery of locomotion was associated with the spontaneous recovery of ChAT and Shh expression. Moreover, we observed a cell proliferation within the depleted SC parenchyma, which was associated with a visible increase of GFAP-positive astrocytes in the same area. Colocalization studies showed that the majority of these proliferating cells are active astrocytes. We hypothesized that Shh expression could have a role in both SC plasticity and the observed glial reaction after neurotoxic lesion. The restoration of normal levels of Shh during the first days after lesion could be a way to partially inhibit glial reaction and to improve functional recovery.
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