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Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice

Alzheimer’s disease (AD) is a neurodegenerative disorder in which the amyloid-β (Aβ) oligomers are a key factor in synaptic impairment and in spatial memory decline associated with neuronal dysfunction. This impairment includes synaptic failure associated with the loss of synaptic proteins that cont...

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Autores principales: Serrano, Felipe G, Tapia-Rojas, Cheril, Carvajal, Francisco J, Hancke, Juan, Cerpa, Waldo, Inestrosa, Nibaldo C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414355/
https://www.ncbi.nlm.nih.gov/pubmed/25524173
http://dx.doi.org/10.1186/1750-1326-9-61
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author Serrano, Felipe G
Tapia-Rojas, Cheril
Carvajal, Francisco J
Hancke, Juan
Cerpa, Waldo
Inestrosa, Nibaldo C
author_facet Serrano, Felipe G
Tapia-Rojas, Cheril
Carvajal, Francisco J
Hancke, Juan
Cerpa, Waldo
Inestrosa, Nibaldo C
author_sort Serrano, Felipe G
collection PubMed
description Alzheimer’s disease (AD) is a neurodegenerative disorder in which the amyloid-β (Aβ) oligomers are a key factor in synaptic impairment and in spatial memory decline associated with neuronal dysfunction. This impairment includes synaptic failure associated with the loss of synaptic proteins that contribute to AD progression. Interestingly, the use of natural compounds is an emergent conceptual strategy in the search for drugs with therapeutic potentials for treating neurodegenerative disorders. In the present study, we report that andrographolide (ANDRO), which is a labdane diterpene extracted from Andrographis paniculata, increases slope of field excitatory postsynaptic potentials (fEPSP) in the CA1 region of hippocampal slices and inhibits long-term depression (LTD), protecting the long-term potentiation (LTP) against the damage induced by Aβ oligomers in vitro, most likely by inhibiting glycogen synthase kinase-3β (GSK-3β). Additionally, ANDRO prevents changes in neuropathology in two different age groups (7- and 12-month-old mice) of an AβPPswe/PS-1 Alzheimer’s model. ANDRO reduces the Aβ levels, changing the ontogeny of amyloid plaques in hippocampi and cortices in 7-month-old mice, and reduces tau phosphorylation around the Aβ oligomeric species in both age groups. Additionally, we observed that ANDRO recovers spatial memory functions that correlate with protecting synaptic plasticity and synaptic proteins in two different age groups. Our results suggest that ANDRO could be used in a potential preventive therapy during AD progression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1750-1326-9-61) contains supplementary material, which is available to authorized users.
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spelling pubmed-44143552015-04-30 Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice Serrano, Felipe G Tapia-Rojas, Cheril Carvajal, Francisco J Hancke, Juan Cerpa, Waldo Inestrosa, Nibaldo C Mol Neurodegener Research Article Alzheimer’s disease (AD) is a neurodegenerative disorder in which the amyloid-β (Aβ) oligomers are a key factor in synaptic impairment and in spatial memory decline associated with neuronal dysfunction. This impairment includes synaptic failure associated with the loss of synaptic proteins that contribute to AD progression. Interestingly, the use of natural compounds is an emergent conceptual strategy in the search for drugs with therapeutic potentials for treating neurodegenerative disorders. In the present study, we report that andrographolide (ANDRO), which is a labdane diterpene extracted from Andrographis paniculata, increases slope of field excitatory postsynaptic potentials (fEPSP) in the CA1 region of hippocampal slices and inhibits long-term depression (LTD), protecting the long-term potentiation (LTP) against the damage induced by Aβ oligomers in vitro, most likely by inhibiting glycogen synthase kinase-3β (GSK-3β). Additionally, ANDRO prevents changes in neuropathology in two different age groups (7- and 12-month-old mice) of an AβPPswe/PS-1 Alzheimer’s model. ANDRO reduces the Aβ levels, changing the ontogeny of amyloid plaques in hippocampi and cortices in 7-month-old mice, and reduces tau phosphorylation around the Aβ oligomeric species in both age groups. Additionally, we observed that ANDRO recovers spatial memory functions that correlate with protecting synaptic plasticity and synaptic proteins in two different age groups. Our results suggest that ANDRO could be used in a potential preventive therapy during AD progression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1750-1326-9-61) contains supplementary material, which is available to authorized users. BioMed Central 2014-12-18 /pmc/articles/PMC4414355/ /pubmed/25524173 http://dx.doi.org/10.1186/1750-1326-9-61 Text en © Serrano et al.; licensee BioMed Central. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Serrano, Felipe G
Tapia-Rojas, Cheril
Carvajal, Francisco J
Hancke, Juan
Cerpa, Waldo
Inestrosa, Nibaldo C
Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice
title Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice
title_full Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice
title_fullStr Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice
title_full_unstemmed Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice
title_short Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice
title_sort andrographolide reduces cognitive impairment in young and mature aβppswe/ps-1 mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414355/
https://www.ncbi.nlm.nih.gov/pubmed/25524173
http://dx.doi.org/10.1186/1750-1326-9-61
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