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

Abstract

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.

Molecular and biophysical features of hippocampal “lipid rafts aging” are modified by dietary n‐3 long‐chain polyunsaturated fatty acids

“…mice, but outcomes from control 6M mice were indistinguishable from 6M or 15M LCPUFA groups (Taoro-González et al, 2022),…”

“…These findings are physiologically relevant, since the lower proportion of the n-6 series, mainly AA, would reduce the potential generation of proinflammatory mediators in the hippocampus(Stables & Gilroy, 2011). Previously, we have observed that dietary n-3 LCPUFA supply reduced age-associated signs of neuroinflammation(Taoro-González et al, 2022).…”

Age-Dependent Changes in Nrf2/Keap1 and Target Antioxidant Protein Expression Correlate to Lipoxidative Adducts, and Are Modulated by Dietary N-3 LCPUFA in the Hippocampus of Mice

“…The same dietary administration schedule was used in our previous study aimed at analyzing the modulatory effects of LCPUFA on hippocampal dysfunction associated with aging. The nutritional content of the respective diets and the detailed schedule for administration can be found in Taoro-Gonzalez et al, 2022 [44]. Accordingly, the main difference between diets lay in the supplementation with 2.1:1 (0.56 mg EPA/kg diet: 0.26 mg DHA/kg diet) of the LCPUFA diet.…”

Emerging Evidence on Membrane Estrogen Receptors as Novel Therapeutic Targets for Central Nervous System Pathologies

“…Recent studies have shown that dietary long-chain polyunsaturated fatty acid (LCPUFA) supplementation improves spatial and recognition memory in aging female mice [ 151 ]. During aging, brain lipid composition changes affect lipid raft integrity and may impair memory function.…”