title: Dietary DHA supplementation causes selective changes in phospholipids from different brain regions in both wild type mice and the Tg2576 mouse model of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is of major concern in ageing populations and we have used the Tg2576 mouse model to understand connections between brain lipids and amyloid pathology. Because dietary docosahexaenoic acid (DHA) has been identified as beneficial, we compared mice fed with a DHA-supplemented diet to those on a nutritionally-sufficient diet. Major phospholipids from cortex, hippocampus and cerebellum were separated and analysed. Each phosphoglyceride had a characteristic fatty acid composition which was similar in cortex and hippocampus but different in the cerebellum. The biggest changes on DHA-supplementation were within ethanolamine phospholipids which, together with phosphatidylserine, had the highest proportions of DHA. Reciprocal alterations in DHA and arachidonate were found. The main diet-induced alterations were found in ethanolamine phospholipids, (and included their ether derivatives), as were the changes observed due to genotype. Tg mice appeared more sensitive to diet with generally lower DHA percentages when on the standard diet and higher relative proportions of DHA when the diet was supplemented. All four major phosphoglycerides analysed showed age-dependent decreases in polyunsaturated fatty acid contents. These data provide, for the first time, a detailed evaluation of phospholipids in different brain areas previously shown to be relevant to behaviour in the Tg2576 mouse model for AD. The lipid changes observed with genotype are consistent with the subtle alterations found in AD patients, especially for the ethanolamine phospholipid molecular species. They also emphasise the contrasting changes in fatty acid content induced by DHA supplementation within individual phospholipid classes.
authors.affiliation: School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK; School of Psychology, Cardiff University, Cardiff CF10 3AT, UK.
authors.forename: Cécile
authors.initials: C
authors.lastname: Bascoul-Colombo
authors.affiliation: School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Guschina
authors.affiliation: School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Maskrey
authors.affiliation: School of Psychology, Cardiff University, Cardiff CF10 3AT, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Good
authors.affiliation: School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: Valerie B
authors.initials: VB
authors.lastname: O'Donnell
authors.affiliation: School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK. Electronic address: Harwood@cardiff.ac.uk.
authors.forename: John L
authors.initials: JL
authors.lastname: Harwood
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D056148:Chromatography, Reverse-Phase / Q000379:methods; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D020404:Glycerophospholipids / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008822:Mice, Transgenic; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D005227:Fatty Acids; D020404:Glycerophospholipids; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D010743:Phospholipids; D004281:Docosahexaenoic Acids; C483858:phosphatidylethanolamine
keywords: 2576 mouse model; Alzheimer's disease; Brain areas; DHA-enriched diet; Phospholipid lipidomics