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The recovery of locomotion after lumbar spinal cord motoneuron depletion is affected by the modulation of Sonic Hedgehog and Notch-1 pathways

Gulino R, Gulisano M (2010) The recovery of locomotion after lumbar spinal cord motoneuron depletion is affected by the modulation of Sonic Hedgehog and Notch-1 pathways. Neuroscience 2010 Abstracts 259.19/W12. Society for Neuroscience, San Diego, CA.

Summary: Sonic hedgehog (Shh) and Notch-1 are involved in the regulation of stem cell function. Additionally, Notch-1 has a role as modulator of synaptic plasticity. In our previous work, we injected Cholera toxin-B saporin (CTB-sap) into the gastrocnemius muscle to induce a selective depletion of motoneurons within lumbar mice spinal cord (SC) and analysed the expression levels of Shh, Notch-1, Numb, Choline acetyltransferase (ChAT) and Synapsin-I proteins. The functional outcome of the lesion was monitored by grid walk test and rotarod. Shh and Notch-1 appeared reduced in the lesioned tissue and correlated with ChAT and Synapsin-I levels, suggesting a role in modulating synaptic plasticity. Numb expression was also reduced after lesion and appeared correlated with motor performance but not with synaptic plasticity. We sought to determine if the pharmacological manipulation of the expression of Shh and Notch-1 could affect functional recovery by a mechanism involving synaptic plasticity. Therefore, we used CTB-sap to induce lesion as above, and injected Cyclopamine, recombinant Shh or recombinant DLL4 chronically into the intrathecal space by means of osmotic minipumps for two weeks. The functional recovery was monitored for one month after lesion by means of grid walk test, two times a week, whereas the modifications of Shh, Notch-1, ChAT and Synapsin-I protein expression levels were measured by western blot and immunohistochemistry. Here, we show that the modulation of Shh or Notch-1 pathways could affect the recovery of locomotion. Moreover, the molecular mechanisms underlying this process is discussed.

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