Jens Randel Nyengaard

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

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Biochemical and cognitive effects of docosahexaenoic acid differ in a developmental and SorLA dependent manner. / Højland, Anne; Richner, Mette; Mølgaard, Simon; Dieu, Ruthe Storgaard; Eskelund, Amanda; Nykjær, Anders; Nyengaard, Jens Randel; Lykkesfeldt, Jens; Glerup, Simon; Nielsen, Morten Schallburg.

In: Behavioural Brain Research, Vol. 348, 01.08.2018, p. 90-100.

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@article{ec0c4896c30a41e3b8f6ef2c7de53fe5,
title = "Biochemical and cognitive effects of docosahexaenoic acid differ in a developmental and SorLA dependent manner",
abstract = "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.",
keywords = "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",
author = "Anne H{\o}jland and Mette Richner and Simon M{\o}lgaard and Dieu, {Ruthe Storgaard} and Amanda Eskelund and Anders Nykj{\ae}r and Nyengaard, {Jens Randel} and Jens Lykkesfeldt and Simon Glerup and Nielsen, {Morten Schallburg}",
note = "Copyright {\textcopyright} 2018 Elsevier B.V. All rights reserved.",
year = "2018",
month = aug,
day = "1",
doi = "10.1016/j.bbr.2018.04.017",
language = "English",
volume = "348",
pages = "90--100",
journal = "Behavioural Brain Research",
issn = "0166-4328",
publisher = "Elsevier BV",

}

RIS

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

N1 - Copyright © 2018 Elsevier B.V. All rights reserved.

PY - 2018/8/1

Y1 - 2018/8/1

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

KW - Docosahexaenoic Acids/pharmacology

KW - Mice, Inbred C57BL

KW - Male

KW - Fatty Acids, Omega-3/metabolism

KW - Membrane Transport Proteins/genetics

KW - Mice, Knockout

KW - Animals

KW - Diet

KW - Cognition/drug effects

KW - Hippocampus/metabolism

KW - Mice

KW - Maze Learning/drug effects

KW - Receptors, LDL/genetics

KW - Dietary Supplements

KW - Brain/metabolism

U2 - 10.1016/j.bbr.2018.04.017

DO - 10.1016/j.bbr.2018.04.017

M3 - Journal article

C2 - 29660442

VL - 348

SP - 90

EP - 100

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

ER -