title: The C-terminal domain of tetanus toxin protects motoneurons against acute excitotoxic damage on spinal cord organotypic cultures.
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.
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Institut de Neurociències and CIBERNED, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Herrando-Grabulosa
authors.forename: Caty
authors.initials: C
authors.lastname: Casas
authors.forename: José
authors.initials: J
authors.lastname: Aguilera
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001343:Autophagy / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000633:toxicity*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009046:Motor Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000166:cytology; D013744:Tetanus Toxin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D018698:Glutamic Acid; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D008869:Microtubule-Associated Proteins; D009498:Neurotoxins; D013744:Tetanus Toxin; C526109:Anxa3 protein, rat; C000605508:Gsk3b protein, rat