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Deuterium‐reinforced polyunsaturated fatty acids improve cognition in a mouse model of sporadic Alzheimer's disease
Author(s) -
Elharram Ahmed,
Czegledy Nicole M.,
Golod Michael,
Milne Ginger L.,
Pollock Erik,
Bennett Brian M.,
Shchepinov Mikhail S.
Publication year - 2017
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14291
Subject(s) - polyunsaturated fatty acid , oxidative stress , lipid peroxidation , medicine , endocrinology , cognitive decline , chemistry , biochemistry , disease , fatty acid , dementia
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‐ PUFA s) are more resistant to the reactive oxygen species‐initiated chain reaction of LPO than regular hydrogenated (H‐) PUFA s. 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‐ PUFA s for 18 weeks. D‐ PUFA treatment markedly decreased cortex and hippocampus F 2 ‐isoprostanes by approximately 55% and prostaglandin F 2α by 20–25% as compared to H‐ PUFA treatment. D‐ PUFA s 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‐ PUFA s therefore represent a promising new strategy to broadly reduce rates of LPO , and combat cognitive decline in AD .