Effects of Dietary n-3 LCPUFA Supplementation on the Hippocampus of Aging Female Mice: Impact on Memory, Lipid Raft-Associated Glutamatergic Receptors and Neuroinflammation

• Published in: International journal of molecular sciences 2022-07, Vol.23 (13), p.7430
• Main Authors: Taoro-González, Lucas, Pereda, Daniel, Valdés-Baizabal, Catalina, González-Gómez, Miriam, Pérez, José A, Mesa-Herrera, Fátima, Canerina-Amaro, Ana, Pérez-González, Herminia, Rodríguez, Covadonga, Díaz, Mario, Marin, Raquel
• Format: Article
• Language: English
• Subjects: Age; Aging; Aging (artificial); Aging - metabolism; Alzheimer's disease; Animal cognition; Animals; Brain; Cognitive ability; Composition; Cytokines; Diet; Dietary Supplements; Estrogen receptors; Estrogens; Fatty Acids - metabolism; Fatty Acids, Omega-3 - metabolism; Fatty Acids, Omega-3 - pharmacology; Fatty Acids, Unsaturated - metabolism; Female; Females; Glutamatergic transmission; Hippocampus; Hippocampus - metabolism; Inflammation; Investigations; Lipid composition; Lipid rafts; Lipids; long-chain polyunsaturated fatty acids supplementation; Membrane Microdomains - metabolism; Memory; Mice; Microenvironments; Molecular interactions; Neural stem cells; Neurogenesis; neuroinflammation; Neuroinflammatory Diseases; Polyunsaturated fatty acids; Proteins; Rafts; Spatial memory; Tumor necrosis factor-TNF
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23137430

Long-chain polyunsaturated fatty acids (LCPUFA), essential molecules whose precursors must be dietary supplied, are highly represented in the brain contributing to numerous neuronal processes. Recent findings have demonstrated that LCPUFA are represented in lipid raft microstructures, where they favor molecular interactions of signaling complexes underlying neuronal functionality. During aging, the brain lipid composition changes affecting the lipid rafts' integrity and protein signaling, which may induce memory detriment. We investigated the effect of a n-3 LCPUFA-enriched diet on the cognitive function of 6- and 15-months-old female mice. Likewise, we explored the impact of dietary n-3 LCPUFAs on hippocampal lipid rafts, and their potential correlation with aging-induced neuroinflammation. Our results demonstrate that n-3 LCPUFA supplementation improves spatial and recognition memory and restores the expression of glutamate and estrogen receptors in the hippocampal lipid rafts of aged mice to similar profiles than young ones. Additionally, the n-3 LCPUFA-enriched diet stabilized the lipid composition of the old mice's hippocampal lipid rafts to the levels of young ones and reduced the aged-induced neuroinflammatory markers. Hence, we propose that n-3 LCPUFA supplementation leads to beneficial cognitive performance by "rejuvenating" the lipid raft microenvironment that stabilizes the integrity and interactions of memory protein players embedded in these microdomains.