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

Authors

  • Mireia Herrando-Grabulosa,

    1. Departament de Bioquímica i Biologia Molecular, Institut de Neurociències and CIBERNED, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain
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  • Caty Casas,

    1. Departament de Biologia Cel·lular, Fisiologia i Immunologia, Institut de Neurociències and CIBERNED, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain
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  • José Aguilera

    Corresponding author
    • Departament de Bioquímica i Biologia Molecular, Institut de Neurociències and CIBERNED, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain
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Address correspondence and reprint requests to José Aguilera; Departament de Bioquímica i Biologia Molecular, Edifici M, Universitat Autònoma de Barcelona, Cerdanyola del Vallès 08193, Barcelona, Spain. E-mail: jose.aguilera@uab.cat

Abstract

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.

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