Docosahexaenoic acid ameliorates contextual fear memory deficits in the Tg2576 Alzheimer's disease mouse model: cellular and molecular correlates
Keywords: 
Alzheimer's disease
DHA
Synapse
Issue Date: 
2023
Project: 
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-104921RB-I00/ES/ESTUDIO DE LA FUNCION DE PLA2G4E EN PLASTICIDAD CEREBRAL Y EN LA RESILIENCIA COGNITIVA. NUEVA ESTRATEGIA PARA EL TRATAMIENTO DE LA ENFERMEDAD DE ALZHEIMER
ISSN: 
1999-4923
Note: 
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license
Citation: 
Badesso, S. (Sara); Cartas-Cejudo, P.; Espelosín-Azpilicueta, M. (María); et al. "Docosahexaenoic acid ameliorates contextual fear memory deficits in the Tg2576 Alzheimer's disease mouse model: cellular and molecular correlates". Pharmaceutics. 15 (1), 2023, 82
Abstract
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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