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Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice

BACKGROUND: In recent years, mechanistic, epidemiologic, and interventional studies have indicated beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) against brain aging and age-related cognitive decline, with the most consistent effects against Alzheimer’s disease (AD) confined es...

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Autores principales: Cutuli, Debora, Landolfo, Eugenia, Nobili, Annalisa, De Bartolo, Paola, Sacchetti, Stefano, Chirico, Doriana, Marini, Federica, Pieroni, Luisa, Ronci, Maurizio, D’Amelio, Marcello, D’Amato, Francesca Romana, Farioli-Vecchioli, Stefano, Petrosini, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667851/
https://www.ncbi.nlm.nih.gov/pubmed/33198763
http://dx.doi.org/10.1186/s13195-020-00705-3
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author Cutuli, Debora
Landolfo, Eugenia
Nobili, Annalisa
De Bartolo, Paola
Sacchetti, Stefano
Chirico, Doriana
Marini, Federica
Pieroni, Luisa
Ronci, Maurizio
D’Amelio, Marcello
D’Amato, Francesca Romana
Farioli-Vecchioli, Stefano
Petrosini, Laura
author_facet Cutuli, Debora
Landolfo, Eugenia
Nobili, Annalisa
De Bartolo, Paola
Sacchetti, Stefano
Chirico, Doriana
Marini, Federica
Pieroni, Luisa
Ronci, Maurizio
D’Amelio, Marcello
D’Amato, Francesca Romana
Farioli-Vecchioli, Stefano
Petrosini, Laura
author_sort Cutuli, Debora
collection PubMed
description BACKGROUND: In recent years, mechanistic, epidemiologic, and interventional studies have indicated beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) against brain aging and age-related cognitive decline, with the most consistent effects against Alzheimer’s disease (AD) confined especially in the early or prodromal stages of the pathology. In the present study, we investigated the action of n-3 PUFA supplementation on behavioral performances and hippocampal neurogenesis, volume, and astrogliosis in aged mice subjected to a selective depletion of basal forebrain cholinergic neurons. Such a lesion represents a valuable model to mimic one of the most reliable hallmarks of early AD neuropathology. METHODS: Aged mice first underwent mu-p75-saporin immunotoxin intraventricular lesions to obtain a massive cholinergic depletion and then were orally supplemented with n-3 PUFA or olive oil (as isocaloric control) for 8 weeks. Four weeks after the beginning of the dietary supplementation, anxiety levels as well as mnesic, social, and depressive-like behaviors were evaluated. Subsequently, hippocampal morphological and biochemical analyses and n-3 PUFA brain quantification were carried out. RESULTS: The n-3 PUFA treatment regulated the anxiety alterations and reverted the novelty recognition memory impairment induced by the cholinergic depletion in aged mice. Moreover, n-3 PUFA preserved hippocampal volume, enhanced neurogenesis in the dentate gyrus, and reduced astrogliosis in the hippocampus. Brain levels of n-3 PUFA were positively related to mnesic abilities. CONCLUSIONS: The demonstration that n-3 PUFA are able to counteract behavioral deficits and hippocampal neurodegeneration in cholinergically depleted aged mice promotes their use as a low-cost, safe nutraceutical tool to improve life quality at old age, even in the presence of first stages of AD.
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spelling pubmed-76678512020-11-17 Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice Cutuli, Debora Landolfo, Eugenia Nobili, Annalisa De Bartolo, Paola Sacchetti, Stefano Chirico, Doriana Marini, Federica Pieroni, Luisa Ronci, Maurizio D’Amelio, Marcello D’Amato, Francesca Romana Farioli-Vecchioli, Stefano Petrosini, Laura Alzheimers Res Ther Research BACKGROUND: In recent years, mechanistic, epidemiologic, and interventional studies have indicated beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) against brain aging and age-related cognitive decline, with the most consistent effects against Alzheimer’s disease (AD) confined especially in the early or prodromal stages of the pathology. In the present study, we investigated the action of n-3 PUFA supplementation on behavioral performances and hippocampal neurogenesis, volume, and astrogliosis in aged mice subjected to a selective depletion of basal forebrain cholinergic neurons. Such a lesion represents a valuable model to mimic one of the most reliable hallmarks of early AD neuropathology. METHODS: Aged mice first underwent mu-p75-saporin immunotoxin intraventricular lesions to obtain a massive cholinergic depletion and then were orally supplemented with n-3 PUFA or olive oil (as isocaloric control) for 8 weeks. Four weeks after the beginning of the dietary supplementation, anxiety levels as well as mnesic, social, and depressive-like behaviors were evaluated. Subsequently, hippocampal morphological and biochemical analyses and n-3 PUFA brain quantification were carried out. RESULTS: The n-3 PUFA treatment regulated the anxiety alterations and reverted the novelty recognition memory impairment induced by the cholinergic depletion in aged mice. Moreover, n-3 PUFA preserved hippocampal volume, enhanced neurogenesis in the dentate gyrus, and reduced astrogliosis in the hippocampus. Brain levels of n-3 PUFA were positively related to mnesic abilities. CONCLUSIONS: The demonstration that n-3 PUFA are able to counteract behavioral deficits and hippocampal neurodegeneration in cholinergically depleted aged mice promotes their use as a low-cost, safe nutraceutical tool to improve life quality at old age, even in the presence of first stages of AD. BioMed Central 2020-11-16 /pmc/articles/PMC7667851/ /pubmed/33198763 http://dx.doi.org/10.1186/s13195-020-00705-3 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.
spellingShingle Research
Cutuli, Debora
Landolfo, Eugenia
Nobili, Annalisa
De Bartolo, Paola
Sacchetti, Stefano
Chirico, Doriana
Marini, Federica
Pieroni, Luisa
Ronci, Maurizio
D’Amelio, Marcello
D’Amato, Francesca Romana
Farioli-Vecchioli, Stefano
Petrosini, Laura
Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice
title Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice
title_full Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice
title_fullStr Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice
title_full_unstemmed Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice
title_short Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice
title_sort behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667851/
https://www.ncbi.nlm.nih.gov/pubmed/33198763
http://dx.doi.org/10.1186/s13195-020-00705-3
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