期刊
FEBS JOURNAL
卷 284, 期 23, 页码 4083-4095出版社
WILEY
DOI: 10.1111/febs.14291
关键词
Alzheimer's disease; cognition; deuterium-based therapeutics; lipid peroxidation; polyunsaturated fatty acid
资金
- The Alzheimer's Society Research Program [365170]
- CIHR Canadian Vascular Network grant [395023]
- NIH [DK020593]
Oxidative damage resulting from increased lipid peroxidation (LPO) is considered an important factor in the development of late onset/age-related Alzheimer's disease (AD). Deuterium-reinforced polyunsaturated fatty acids (D-PUFAs) are more resistant to the reactive oxygen species-initiated chain reaction of LPO than regular hydrogenated (H-) PUFAs. We investigated the effect of D-PUFA treatment on LPO and cognitive performance in aldehyde dehydrogenase 2 (Aldh2) null mice, an established model of oxidative stress-related cognitive impairment that exhibits AD-like pathologies. Mice were fed a Western-type diet containing either D- or H-PUFAs for 18 weeks. D-PUFA treatment markedly decreased cortex and hippocampus F-2-isoprostanes by approximately 55% and prostaglandin F-2 by 20-25% as compared to H-PUFA treatment. D-PUFAs consistently improved performance in cognitive/memory tests, essentially resetting performance of the D-PUFA-fed Aldh2(-/-) mice to that of wild-type mice fed a typical laboratory diet. D-PUFAs therefore represent a promising new strategy to broadly reduce rates of LPO, and combat cognitive decline in AD.
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