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dc.contributor.author
Iulita, M. Florencia
dc.contributor.author
Bistue Millon, Maria Beatriz
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dc.contributor.author
Pentz, Rowan
dc.contributor.author
Aguilar, Lisi Flores
dc.contributor.author
Do Carmo, Sonia
dc.contributor.author
Allard, Simon
dc.contributor.author
Michalski, Bernadeta
dc.contributor.author
Wilson, Edward N.
dc.contributor.author
Ducatenzeiler, Adriana
dc.contributor.author
Bruno, Martin
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dc.contributor.author
Fahnestock, Margaret
dc.contributor.author
Cuello, A. Claudio
dc.date.available
2019-02-01T19:44:40Z
dc.date.issued
2017-12
dc.identifier.citation
Iulita, M. Florencia; Bistue Millon, Maria Beatriz; Pentz, Rowan; Aguilar, Lisi Flores; Do Carmo, Sonia; et al.; Differential deregulation of NGF and BDNF neurotrophins in a transgenic rat model of Alzheimer's disease; Academic Press Inc Elsevier Science; Neurobiology of Disease; 108; 12-2017; 307-323
dc.identifier.issn
0969-9961
dc.identifier.uri
http://hdl.handle.net/11336/69227
dc.description.abstract
Evidence from human neuropathological studies indicates that the levels of the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are compromised in Alzheimer's disease. However, the causes and temporal (pathology-dependent) evolution of these alterations are not completely understood. To elucidate these issues, we investigated the McGill-R-Thy1-APP transgenic rat, which exhibits progressive intracellular and extracellular amyloid-beta (Aβ) pathology and ensuing cognitive deficits. Neurochemical analyses revealed a differential dysregulation of NGF and BDNF transcripts and protein expression. While BDNF mRNA levels were significantly reduced at very early stages of amyloid pathology, before plaques appeared, there were no changes in NGF mRNA expression even at advanced stages. Paradoxically, the protein levels of the NGF precursor were increased. These changes in neurotrophin expression are identical to those seen during the progression of Alzheimer's disease. At advanced pathological stages, deficits in the protease cascade controlling the maturation and degradation of NGF were evident in McGill transgenic rats, in line with the paradoxical upregulation of proNGF, as seen in Alzheimer's disease, in the absence of changes in NGF mRNA. The compromise in NGF metabolism and BDNF levels was accompanied by downregulation of cortical cholinergic synapses; strengthening the evidence that neurotrophin dysregulation affects cholinergic synapses and synaptic plasticity. Our findings suggest a differential temporal deregulation of NGF and BDNF neurotrophins, whereby deficits in BDNF mRNA appear at early stages of intraneuronal Aβ pathology, before alterations in NGF metabolism and cholinergic synapse loss manifest.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Academic Press Inc Elsevier Science
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Alzheimer'S Disease
dc.subject
Amyloid-Β
dc.subject
Bdnf
dc.subject
Cholinergic
dc.subject
Mmp-9
dc.subject
Nerve Growth Factor
dc.subject
Neuroserpin
dc.subject
Neurotrophins
dc.subject
Prongf
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Synaptic Plasticity
dc.subject
Tpa
dc.subject.classification
Otras Ciencias Biológicas
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Differential deregulation of NGF and BDNF neurotrophins in a transgenic rat model of Alzheimer's disease
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-01-31T14:10:57Z
dc.journal.volume
108
dc.journal.pagination
307-323
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Iulita, M. Florencia. McGill University; Canadá
dc.description.fil
Fil: Bistue Millon, Maria Beatriz. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Pentz, Rowan. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; Argentina
dc.description.fil
Fil: Aguilar, Lisi Flores. McGill University; Canadá
dc.description.fil
Fil: Do Carmo, Sonia. McGill University; Canadá
dc.description.fil
Fil: Allard, Simon. McGill University; Canadá
dc.description.fil
Fil: Michalski, Bernadeta. Mc Master University; Canadá
dc.description.fil
Fil: Wilson, Edward N.. McGill University; Canadá
dc.description.fil
Fil: Ducatenzeiler, Adriana. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; Argentina
dc.description.fil
Fil: Bruno, Martin. Universidad Católica de Cuyo - Sede San Juan. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Fahnestock, Margaret. Mc Master University; Canadá
dc.description.fil
Fil: Cuello, A. Claudio. McGill University; Canadá
dc.journal.title
Neurobiology of Disease
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.nbd.2017.08.019
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0969996117302097
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