Deuterated polyunsaturated fatty acids reduce brain lipid peroxidation and hippocampal amyloid beta-peptide levels, without discernable behavioral effects in an APP/PS1 mutant transgenic mouse model of Alzheimer's disease

作者：Raefsky Sophia M; Furman Ran; Milne Ginger; Pollock Erik; Axelsen Paul; Mattson Mark P^*; Shchepinov Mikhail S

来源：Neurobiology of Aging, 2018, 66: 165-176.

DOI：10.1016/j.neurobiolaging.2018.02.024

• Amyloid
• Hippocampus
• Hydroxynonenal
• Learning and memory
• Lipid peroxidation
• PUFA

Alzheimer's disease (AD) involves progressive deposition of amyloid beta-peptide (A beta), synapse loss, and neuronal death, which occur in brain regions critical for learning and memory. Considerable evidence suggests that lipid peroxidation contributes to synaptic dysfunction and neuronal degeneration, both upstream and downstream of A beta pathology. Recent findings suggest that lipid peroxidation can be inhibited by replacement of polyunsaturated fatty acids (PUFA) with isotope-reinforced (deuterated) PUFA (D-PUFA), and that D-PUFA can protect neurons in experimental models of Parkinson's disease. Here, we determined whether dietary D-PUFA would ameliorate A beta pathology and/or cognitive deficits in a mouse model of AD (amyloid precursor protein/presenilin 1 double mutant transgenic mice). The D-PUFA diet did not ameliorate spatial learning and memory deficits in the AD mice. Compared to mice fed an hydrogenated-PUFA control diet, those fed D-PUFA for 5 months exhibited high levels of incorporation of deuterium into arachidonic acid and docosahexaenoic acid, and reduced concentrations of lipid peroxidation products (F2 isoprostanes and neuroprostanes), in the brain tissues. Concentrations of A beta 40 and A beta 38 in the hippocampus were significantly lower, with a trend to reduced concentrations of A beta 42, in mice fed D-PUFA compared to those fed hydrogenated-PUFA. We conclude that a D-PUFA diet reduces the brain tissue concentrations of both arachidonic acid and docosahexaenoic acid oxidation products, as well as the concentration of A beta s. Published by Elsevier Inc.

• 出版日期2018-6