Early-stage inflammation and experimental therapy in transgenic models of the Alzheimer-like amyloid pathology

Autores
Cuello, A.C.; Ferretti, M.T.; Leon, W.C.; Iulita, M.F.; Melis, T.; Ducatenzeiler, A.; Bruno, Martin; Canneva, F.
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Intracellular accumulation of β-amyloid (Aβ) is one of the early features in the neuropathology of Alzheimer's disease (AD) and Down's syndrome. This can be reproduced in cell and transgenic animal models of the AD-like amyloid pathology. In a transgenic rat model, our lab has previously shown that the intracellular accumulation of Aβ is sufficient to provoke cognitive impairments and biochemical alterations in the cerebral cortex and hippocampus in the absence of amyloid plaques. Objective: To investigate an early, pre-plaque inflammatory process in AD-like transgenic models and establish whether the neurotoxic effects of Aβ oligomers and proinflammatory responses can be arrested with minocycline. Methods: For these studies, we used naïve mice and transgenic animal models of the AD-like amyloid pathology and applied neurochemical, immunohistochemical and behavioral experimental approaches. Results: In the early stages of the AD-like amyloid pathology, intracellular Aβ oligomers accumulate within neurons of the cerebral cortex and hippocampus. Coincidental with this, behavioral impairments occur prior to the appearance of amyloid plaques, together with an upregulation of MHC-II, i-NOS and COX-2, well-known proinflammatory markers. Treatment with minocycline corrected behavioral impairments, lowered inflammatory markers and levels of Aβ trimers. Conclusion: A pharmacological approach targeting the early neuroinflammatory effects of Aβ might be a promising strategy to prevent or delay the onset of AD.
Fil: Cuello, A.C.. McGill University; Canadá
Fil: Ferretti, M.T.. McGill University; Canadá
Fil: Leon, W.C.. McGill University; Canadá
Fil: Iulita, M.F.. McGill University; Canadá
Fil: Melis, T.. McGill University; Canadá
Fil: Ducatenzeiler, A.. McGill University; Canadá
Fil: Bruno, Martin. McGill University; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Canneva, F.. McGill University; Canadá
Materia
AΒ Oligomers And Minocycline
Alzheimer'S Disease
Central Nervous System
Inflammation
Intracellular AΒ
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/53993
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/53993
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Early-stage inflammation and experimental therapy in transgenic models of the Alzheimer-like amyloid pathologyCuello, A.C.Ferretti, M.T.Leon, W.C.Iulita, M.F.Melis, T.Ducatenzeiler, A.Bruno, MartinCanneva, F.AΒ Oligomers And MinocyclineAlzheimer'S DiseaseCentral Nervous SystemInflammationIntracellular AΒhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Intracellular accumulation of β-amyloid (Aβ) is one of the early features in the neuropathology of Alzheimer's disease (AD) and Down's syndrome. This can be reproduced in cell and transgenic animal models of the AD-like amyloid pathology. In a transgenic rat model, our lab has previously shown that the intracellular accumulation of Aβ is sufficient to provoke cognitive impairments and biochemical alterations in the cerebral cortex and hippocampus in the absence of amyloid plaques. Objective: To investigate an early, pre-plaque inflammatory process in AD-like transgenic models and establish whether the neurotoxic effects of Aβ oligomers and proinflammatory responses can be arrested with minocycline. Methods: For these studies, we used naïve mice and transgenic animal models of the AD-like amyloid pathology and applied neurochemical, immunohistochemical and behavioral experimental approaches. Results: In the early stages of the AD-like amyloid pathology, intracellular Aβ oligomers accumulate within neurons of the cerebral cortex and hippocampus. Coincidental with this, behavioral impairments occur prior to the appearance of amyloid plaques, together with an upregulation of MHC-II, i-NOS and COX-2, well-known proinflammatory markers. Treatment with minocycline corrected behavioral impairments, lowered inflammatory markers and levels of Aβ trimers. Conclusion: A pharmacological approach targeting the early neuroinflammatory effects of Aβ might be a promising strategy to prevent or delay the onset of AD.Fil: Cuello, A.C.. McGill University; CanadáFil: Ferretti, M.T.. McGill University; CanadáFil: Leon, W.C.. McGill University; CanadáFil: Iulita, M.F.. McGill University; CanadáFil: Melis, T.. McGill University; CanadáFil: Ducatenzeiler, A.. McGill University; CanadáFil: Bruno, Martin. McGill University; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Canneva, F.. McGill University; CanadáKarger2010-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/53993Cuello, A.C.; Ferretti, M.T.; Leon, W.C.; Iulita, M.F.; Melis, T.; et al.; Early-stage inflammation and experimental therapy in transgenic models of the Alzheimer-like amyloid pathology; Karger; Neurodegenerative Diseases; 7; 1-3; 4-2010; 96-981660-2854CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1159/000285514info:eu-repo/semantics/altIdentifier/url/https://www.karger.com/Article/Abstract/285514info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:09:03Zoai:ri.conicet.gov.ar:11336/53993instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:09:03.791CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Early-stage inflammation and experimental therapy in transgenic models of the Alzheimer-like amyloid pathology
title Early-stage inflammation and experimental therapy in transgenic models of the Alzheimer-like amyloid pathology
spellingShingle Early-stage inflammation and experimental therapy in transgenic models of the Alzheimer-like amyloid pathology
Cuello, A.C.
AΒ Oligomers And Minocycline
Alzheimer'S Disease
Central Nervous System
Inflammation
Intracellular AΒ
title_short Early-stage inflammation and experimental therapy in transgenic models of the Alzheimer-like amyloid pathology
title_full Early-stage inflammation and experimental therapy in transgenic models of the Alzheimer-like amyloid pathology
title_fullStr Early-stage inflammation and experimental therapy in transgenic models of the Alzheimer-like amyloid pathology
title_full_unstemmed Early-stage inflammation and experimental therapy in transgenic models of the Alzheimer-like amyloid pathology
title_sort Early-stage inflammation and experimental therapy in transgenic models of the Alzheimer-like amyloid pathology
dc.creator.none.fl_str_mv Cuello, A.C.
Ferretti, M.T.
Leon, W.C.
Iulita, M.F.
Melis, T.
Ducatenzeiler, A.
Bruno, Martin
Canneva, F.
author Cuello, A.C.
author_facet Cuello, A.C.
Ferretti, M.T.
Leon, W.C.
Iulita, M.F.
Melis, T.
Ducatenzeiler, A.
Bruno, Martin
Canneva, F.
author_role author
author2 Ferretti, M.T.
Leon, W.C.
Iulita, M.F.
Melis, T.
Ducatenzeiler, A.
Bruno, Martin
Canneva, F.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AΒ Oligomers And Minocycline
Alzheimer'S Disease
Central Nervous System
Inflammation
Intracellular AΒ
topic AΒ Oligomers And Minocycline
Alzheimer'S Disease
Central Nervous System
Inflammation
Intracellular AΒ
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Intracellular accumulation of β-amyloid (Aβ) is one of the early features in the neuropathology of Alzheimer's disease (AD) and Down's syndrome. This can be reproduced in cell and transgenic animal models of the AD-like amyloid pathology. In a transgenic rat model, our lab has previously shown that the intracellular accumulation of Aβ is sufficient to provoke cognitive impairments and biochemical alterations in the cerebral cortex and hippocampus in the absence of amyloid plaques. Objective: To investigate an early, pre-plaque inflammatory process in AD-like transgenic models and establish whether the neurotoxic effects of Aβ oligomers and proinflammatory responses can be arrested with minocycline. Methods: For these studies, we used naïve mice and transgenic animal models of the AD-like amyloid pathology and applied neurochemical, immunohistochemical and behavioral experimental approaches. Results: In the early stages of the AD-like amyloid pathology, intracellular Aβ oligomers accumulate within neurons of the cerebral cortex and hippocampus. Coincidental with this, behavioral impairments occur prior to the appearance of amyloid plaques, together with an upregulation of MHC-II, i-NOS and COX-2, well-known proinflammatory markers. Treatment with minocycline corrected behavioral impairments, lowered inflammatory markers and levels of Aβ trimers. Conclusion: A pharmacological approach targeting the early neuroinflammatory effects of Aβ might be a promising strategy to prevent or delay the onset of AD.
Fil: Cuello, A.C.. McGill University; Canadá
Fil: Ferretti, M.T.. McGill University; Canadá
Fil: Leon, W.C.. McGill University; Canadá
Fil: Iulita, M.F.. McGill University; Canadá
Fil: Melis, T.. McGill University; Canadá
Fil: Ducatenzeiler, A.. McGill University; Canadá
Fil: Bruno, Martin. McGill University; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Canneva, F.. McGill University; Canadá
description Background: Intracellular accumulation of β-amyloid (Aβ) is one of the early features in the neuropathology of Alzheimer's disease (AD) and Down's syndrome. This can be reproduced in cell and transgenic animal models of the AD-like amyloid pathology. In a transgenic rat model, our lab has previously shown that the intracellular accumulation of Aβ is sufficient to provoke cognitive impairments and biochemical alterations in the cerebral cortex and hippocampus in the absence of amyloid plaques. Objective: To investigate an early, pre-plaque inflammatory process in AD-like transgenic models and establish whether the neurotoxic effects of Aβ oligomers and proinflammatory responses can be arrested with minocycline. Methods: For these studies, we used naïve mice and transgenic animal models of the AD-like amyloid pathology and applied neurochemical, immunohistochemical and behavioral experimental approaches. Results: In the early stages of the AD-like amyloid pathology, intracellular Aβ oligomers accumulate within neurons of the cerebral cortex and hippocampus. Coincidental with this, behavioral impairments occur prior to the appearance of amyloid plaques, together with an upregulation of MHC-II, i-NOS and COX-2, well-known proinflammatory markers. Treatment with minocycline corrected behavioral impairments, lowered inflammatory markers and levels of Aβ trimers. Conclusion: A pharmacological approach targeting the early neuroinflammatory effects of Aβ might be a promising strategy to prevent or delay the onset of AD.
publishDate 2010
dc.date.none.fl_str_mv 2010-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/53993
Cuello, A.C.; Ferretti, M.T.; Leon, W.C.; Iulita, M.F.; Melis, T.; et al.; Early-stage inflammation and experimental therapy in transgenic models of the Alzheimer-like amyloid pathology; Karger; Neurodegenerative Diseases; 7; 1-3; 4-2010; 96-98
1660-2854
CONICET Digital
CONICET
url http://hdl.handle.net/11336/53993
identifier_str_mv Cuello, A.C.; Ferretti, M.T.; Leon, W.C.; Iulita, M.F.; Melis, T.; et al.; Early-stage inflammation and experimental therapy in transgenic models of the Alzheimer-like amyloid pathology; Karger; Neurodegenerative Diseases; 7; 1-3; 4-2010; 96-98
1660-2854
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1159/000285514
info:eu-repo/semantics/altIdentifier/url/https://www.karger.com/Article/Abstract/285514
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Karger
publisher.none.fl_str_mv Karger
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846083238184878080
score 13.22299

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