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dc.contributor.author
Danelon, Víctor
dc.contributor.author
Montroull, Laura Ester
dc.contributor.author
Unsain, Nicolas
dc.contributor.author
Barker, Philip A.
dc.contributor.author
Masco, Daniel Hugo
dc.date.available
2018-03-21T22:00:29Z
dc.date.issued
2016-09
dc.identifier.citation
Danelon, Víctor; Montroull, Laura Ester; Unsain, Nicolas; Barker, Philip A.; Masco, Daniel Hugo; Calpain-dependent truncated form of TrkB-FL increases in neurodegenerative processes; Academic Press Inc Elsevier Science; Molecular and Cellular Neuroscience; 75; 9-2016; 81-92
dc.identifier.issn
1044-7431
dc.identifier.uri
http://hdl.handle.net/11336/39600
dc.description.abstract
Recent findings indicate that the mechanisms that drive reshaping of the nervous system are aberrantly activated in epilepsy and several neurodegenerative diseases. The recurrent seizures in epilepsy, particularly in the condition called status epilepticus, can cause permanent neurological damage, resulting in cognitive dysfunction and other serious neurological conditions. In this study, we used an in vitro model of status epilepticus to examine the role of calpain in the degeneration of hippocampal neurons. We grew neurons on a culture system that allowed studying the dendritic and axonal domains separately from the cell bodies. We found that a recently characterized calpain substrate, the neurotrophin receptor TrkB, is cleaved in the dendritic and axonal domain of neurons committed to die, and this constitutes an early step in the neuronal degeneration process. While the full-length TrkB (TrkB-FL) levels decreased, the truncated form of TrkB (Tc TrkB-FL) concurrently increased, leading to a TrkB-FL/Tc TrkB-FL imbalance, which is thought to be causally linked to neurodegeneration. We further show that the treatment with N-acetyl-Leu-Leu-norleucinal, a specific calpain activity blocker, fully protects the neuronal processes from degeneration, prevents the TrkB-FL/Tc TrkB-FL imbalance, and provides full neuroprotection. Moreover, the use of the TrkB antagonist ANA 12 at the time when the levels of TrkB-FL were significantly decreased, totally blocked neuronal death, suggesting that Tc TrkB-FL may have a role in neuronal death. These results indicate that the imbalance of these neurotrophins receptors plays a key role in neurite degeneration induced by seizures.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Academic Press Inc Elsevier Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Calpain
dc.subject
Neurite Degeneration
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Neuronal Death
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Status Epilepticus
dc.subject
Trkb-Fl
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Truncated Trkb-Fl
dc.subject.classification
Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Calpain-dependent truncated form of TrkB-FL increases in neurodegenerative processes
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-03-21T16:28:03Z
dc.journal.volume
75
dc.journal.pagination
81-92
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Danelon, Víctor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
dc.description.fil
Fil: Montroull, Laura Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
dc.description.fil
Fil: Unsain, Nicolas. McGill University; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Barker, Philip A.. McGill University; Canadá
dc.description.fil
Fil: Masco, Daniel Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina
dc.journal.title
Molecular and Cellular Neuroscience
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.mcn.2016.07.002
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1044743116300768
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