Jens Randel Nyengaard

Biochemical and cognitive effects of docosahexaenoic acid differ in a developmental and SorLA dependent manner

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Beneficial effects of omega-3 fatty acid intake on cognition are under debate as some studies show beneficial effects while others show no effects of omega-3 supplementation. These inconsistencies may be a result of inter-individual response variations, potentially caused by gene and diet interactions. SorLA is a multifunctional receptor involved in ligand trafficking including lipoprotein lipase and amyloid precursor protein. Decreased SorLA levels have been correlated to Alzheimer's disease, and omega-3 fatty acid supplementation is known to increase SorLA expression in neuronal cell lines and mouse models. We therefore addressed potential correlations between Sorl1 and dietary omega-3 in SorLA deficient mice (Sorl1-/-) and controls exposed to diets supplemented with or deprived of omega-3 during their entire development and lifespan (lifelong) or solely from the time of weaning (post weaning). Observed diet-induced effects were only evident when exposed to lifelong omega-3 supplementation or deprivation as opposed to post weaning exposure only. Lifelong exposure to omega-3 supplementation resulted in impaired spatial learning in Sorl1-/- mice. The vitamin C antioxidant capacity in the brains of Sorl1-/- mice was reduced, but reduced glutathione and vitamin E levels were increased, leaving the overall antioxidant capacity of the brain inconclusive. No gross morphological differences of hippocampal neurons were found to account for the altered behavior. We found a significant adverse effect in cognitive performance by combining SorLA deficiency with lifelong exposure to omega-3. Our results stress the need for investigations of the underlying molecular mechanisms to clarify the precise circumstances under which omega-3 supplementation may be beneficial.

Original languageEnglish
JournalBehavioural Brain Research
Volume348
Pages (from-to)90-100
Number of pages11
ISSN0166-4328
DOIs
Publication statusPublished - 1 Aug 2018

    Research areas

  • Behavior, Mouse models, Omega-3 fatty acids, Oxidative stress, PUFA, Sorl1, Docosahexaenoic Acids/pharmacology, Mice, Inbred C57BL, Male, Fatty Acids, Omega-3/metabolism, Membrane Transport Proteins/genetics, Mice, Knockout, Animals, Diet, Cognition/drug effects, Hippocampus/metabolism, Mice, Maze Learning/drug effects, Receptors, LDL/genetics, Dietary Supplements, Brain/metabolism

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