Aim: 

Recent strategies to repair the injured spinal cord (SC) relied on the modulation of endogenous neurogenesis and neuroplasticity. Sonic hedgehog (Shh), Notch-1 and Numb are involved in the stem cell functioning, and Notch-1 has also a role in synaptic plasticity. Little is known about the role of these factors in a neurotoxic SC lesion model.

Methods: 

We injected Cholera toxin-B saporin into the gastrocnemius muscle to selectively kill lumbar motoneurons and analysed the expression of Choline acetyltransferase (ChAT), Synapsin-I, Shh, Notch-1 and Numb proteins. The effects of lesion on hindlimb function was monitored by grid walk test and rotarod.

Results: 

The lesion caused a motoneuron depletion and a transient decrease of ChAT, Synapsin-I, Shh and Numb protein levels in the lumbar SC. ChAT was associated with Synapsin-I levels and motor performance, suggesting that the recovery of locomotion could depend from synaptic plasticity. Shh and Notch-1 correlated with Synapsin-I levels, suggesting a role in modulating synaptic plasticity. Numb expression appeared also reduced after lesion and linked to motor performance. We also observed a number of active astrocytes within the depleted SC. Given the role of these proteins in adult neurogenesis, we hypothesized their involvement in the observed glial reaction.

Conclusion: 

The in vivo manipulation of Shh, Notch-1 and Numb signalling after lesion could be a way to improve functional recovery by modulating synaptic plasticity and neurogenesis.