The C‐terminal domain of tetanus toxin protects motoneurons against acute excitotoxic damage on spinal cord organotypic cultures

The C‐terminal domain of tetanus toxin (Hc‐TeTx) has been suggested to act as a neuroprotective agent by activating signaling pathways related to neurotrophins and also to exert anti‐apoptotic effects. Here, we show the beneficial properties of the recombinant protein Hc‐TeTx to protect spinal motoneurons against excitotoxic damage. In vitro spinal cord organotypic cultures were used to assess acute glutamate excitotoxic damage. Our results indicate that Hc‐TeTx treatment improves motoneuron survival within a short therapeutical window (the first 2 h post‐injury). Within this interval, we found that p44/p42 MAP kinase (ERK1/2) and glycogen synthase kinase‐3 (GSK3β) signaling pathways play a crucial role in the neuroprotective effect. Moreover, we demonstrated that Hc–TeTx treatment initiate autophagy which is ERK1/2‐ and GSK3β‐dependent. These findings suggest a possible therapeutical tool to improve motoneuron survival immediately after excitotoxic insults or during the secondary injury phase that occurs after spinal cord trauma.