Aim: 

We used Cholera toxin-B saporin (CTB-sap) to induce a motoneuron depletion within the lumbar spinal cord (SC) and to study the expression levels of Sonic hedgehog (Shh) and the possible cell proliferation and differentiation within the depleted SC of young adult mice. Shh is a secreted glycoprotein 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, which is considered a non-neurogenic district.

Methods: 

ChAT and Shh expression levels was measured by western blotting; cell proliferation and differentiation were analysed by immunohisto-chemistry, by using optical and confocal microscopy. Motor performance was measured by a grid walk test.

Results: 

The injection of CTB-sap into the gastrocnemius muscle, caused a 30% decrease of either motoneuron number and ChAT expression, one week after lesion. Moreover, we found a significant down-regulation of Shh, which correlate with ChAT decrease. Both proteins were restored at one month after lesion. The expression of ChAT also correlate with the grid walk performance. 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 tissue, 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.

Conclusions: 

Shh 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.