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Docosahexaenoic Acid Ameliorates Contextual Fear Memory Deficits in the Tg2576 Alzheimer’s Disease Mouse Model: Cellular and Molecular Correlates

Docosahexaenoic acid (DHA), the most abundant polyunsaturated fatty acid in the brain, is essential for successful aging. In fact, epidemiological studies have demonstrated that increased intake of DHA might lower the risk for developing Alzheimer’s disease (AD). These observations are supported by...

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Autores principales: Badesso, Sara, Cartas-Cejudo, Paz, Espelosin, Maria, Santamaria, Enrique, Cuadrado-Tejedor, Mar, Garcia-Osta, Ana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866126/
https://www.ncbi.nlm.nih.gov/pubmed/36678710
http://dx.doi.org/10.3390/pharmaceutics15010082
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author Badesso, Sara
Cartas-Cejudo, Paz
Espelosin, Maria
Santamaria, Enrique
Cuadrado-Tejedor, Mar
Garcia-Osta, Ana
author_facet Badesso, Sara
Cartas-Cejudo, Paz
Espelosin, Maria
Santamaria, Enrique
Cuadrado-Tejedor, Mar
Garcia-Osta, Ana
author_sort Badesso, Sara
collection PubMed
description Docosahexaenoic acid (DHA), the most abundant polyunsaturated fatty acid in the brain, is essential for successful aging. In fact, epidemiological studies have demonstrated that increased intake of DHA might lower the risk for developing Alzheimer’s disease (AD). These observations are supported by studies in animal models showing that DHA reduces synaptic pathology and memory deficits. Different mechanisms to explain these beneficial effects have been proposed; however, the molecular pathways involved are still unknown. In this study, to unravel the main underlying molecular mechanisms activated upon DHA treatment, the effect of a high dose of DHA on cognitive function and AD pathology was analyzed in aged Tg2576 mice and their wild-type littermates. Transcriptomic analysis of mice hippocampi using RNA sequencing was subsequently performed. Our results revealed that, through an amyloid-independent mechanism, DHA enhanced memory function and increased synapse formation only in the Tg2576 mice. Likewise, the IPA analysis demonstrated that essential neuronal functions related to synaptogenesis, neuritogenesis, the branching of neurites, the density of dendritic spines and the outgrowth of axons were upregulated upon-DHA treatment in Tg2576 mice. Our results suggest that memory function in APP mice is influenced by DHA intake; therefore, a high dose of daily DHA should be tested as a dietary supplement for AD dementia prevention.
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spelling pubmed-98661262023-01-22 Docosahexaenoic Acid Ameliorates Contextual Fear Memory Deficits in the Tg2576 Alzheimer’s Disease Mouse Model: Cellular and Molecular Correlates Badesso, Sara Cartas-Cejudo, Paz Espelosin, Maria Santamaria, Enrique Cuadrado-Tejedor, Mar Garcia-Osta, Ana Pharmaceutics Article Docosahexaenoic acid (DHA), the most abundant polyunsaturated fatty acid in the brain, is essential for successful aging. In fact, epidemiological studies have demonstrated that increased intake of DHA might lower the risk for developing Alzheimer’s disease (AD). These observations are supported by studies in animal models showing that DHA reduces synaptic pathology and memory deficits. Different mechanisms to explain these beneficial effects have been proposed; however, the molecular pathways involved are still unknown. In this study, to unravel the main underlying molecular mechanisms activated upon DHA treatment, the effect of a high dose of DHA on cognitive function and AD pathology was analyzed in aged Tg2576 mice and their wild-type littermates. Transcriptomic analysis of mice hippocampi using RNA sequencing was subsequently performed. Our results revealed that, through an amyloid-independent mechanism, DHA enhanced memory function and increased synapse formation only in the Tg2576 mice. Likewise, the IPA analysis demonstrated that essential neuronal functions related to synaptogenesis, neuritogenesis, the branching of neurites, the density of dendritic spines and the outgrowth of axons were upregulated upon-DHA treatment in Tg2576 mice. Our results suggest that memory function in APP mice is influenced by DHA intake; therefore, a high dose of daily DHA should be tested as a dietary supplement for AD dementia prevention. MDPI 2022-12-27 /pmc/articles/PMC9866126/ /pubmed/36678710 http://dx.doi.org/10.3390/pharmaceutics15010082 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Badesso, Sara
Cartas-Cejudo, Paz
Espelosin, Maria
Santamaria, Enrique
Cuadrado-Tejedor, Mar
Garcia-Osta, Ana
Docosahexaenoic Acid Ameliorates Contextual Fear Memory Deficits in the Tg2576 Alzheimer’s Disease Mouse Model: Cellular and Molecular Correlates
title Docosahexaenoic Acid Ameliorates Contextual Fear Memory Deficits in the Tg2576 Alzheimer’s Disease Mouse Model: Cellular and Molecular Correlates
title_full Docosahexaenoic Acid Ameliorates Contextual Fear Memory Deficits in the Tg2576 Alzheimer’s Disease Mouse Model: Cellular and Molecular Correlates
title_fullStr Docosahexaenoic Acid Ameliorates Contextual Fear Memory Deficits in the Tg2576 Alzheimer’s Disease Mouse Model: Cellular and Molecular Correlates
title_full_unstemmed Docosahexaenoic Acid Ameliorates Contextual Fear Memory Deficits in the Tg2576 Alzheimer’s Disease Mouse Model: Cellular and Molecular Correlates
title_short Docosahexaenoic Acid Ameliorates Contextual Fear Memory Deficits in the Tg2576 Alzheimer’s Disease Mouse Model: Cellular and Molecular Correlates
title_sort docosahexaenoic acid ameliorates contextual fear memory deficits in the tg2576 alzheimer’s disease mouse model: cellular and molecular correlates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866126/
https://www.ncbi.nlm.nih.gov/pubmed/36678710
http://dx.doi.org/10.3390/pharmaceutics15010082
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