TY - JOUR

T1 - Biochemical and cognitive effects of docosahexaenoic acid differ in a developmental and SorLA dependent manner

AU - Højland, Anne

AU - Richner, Mette

AU - Mølgaard, Simon

AU - Dieu, Ruthe Storgaard

AU - Eskelund, Amanda

AU - Nykjær, Anders

AU - Nyengaard, Jens Randel

AU - Lykkesfeldt, Jens

AU - Glerup, Simon

AU - Nielsen, Morten Schallburg

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Behavior

KW - Mouse models

KW - Omega-3 fatty acids

KW - Oxidative stress

KW - PUFA

KW - Sorl1

U2 - 10.1016/j.bbr.2018.04.017

DO - 10.1016/j.bbr.2018.04.017

M3 - Journal article

C2 - 29660442

AN - SCOPUS:85046166934

VL - 348

SP - 90

EP - 100

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

ER -