title: The hydroxylated form of docosahexaenoic acid (DHA-H) modifies the brain lipid composition in a model of Alzheimer's disease, improving behavioral motor function and survival.
abstract: We have compared the effect of the commonly used ω-3 fatty acid, docosahexaenoic acid ethyl ester (DHA-EE), and of its 2-hydroxylated DHA form (DHA-H), on brain lipid composition, behavior and lifespan in a new human transgenic Drosophila melanogaster model of Alzheimer's disease (AD). The transgenic flies expressed human Aβ42 and tau, and the overexpression of these human transgenes in the CNS of these flies produced progressive defects in motor function (antigeotaxic behavior) while reducing the animal's lifespan. Here, we demonstrate that both DHA-EE and DHA-H increase the longer chain fatty acids (≥18C) species in the heads of the flies, although only DHA-H produced an unknown chromatographic peak that corresponded to a non-hydroxylated lipid. In addition, only treatment with DHA-H prevented the abnormal climbing behavior and enhanced the lifespan of these transgenic flies. These benefits of DHA-H were confirmed in the well characterized transgenic PS1/APP mouse model of familial AD (5xFAD mice), mice that develop defects in spatial learning and in memory, as well as behavioral deficits. Hence, it appears that the modulation of brain lipid composition by DHA-H could have remedial effects on AD associated neurodegeneration. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.
authors.affiliation: Laboratory of Molecular Cell Biomedicine, University of the Balearic Islands, Palma, Spain.
authors.forename: Raheem J
authors.initials: RJ
authors.lastname: Mohaibes
authors.affiliation: Laboratory of Molecular Cell Biomedicine, University of the Balearic Islands, Palma, Spain.
authors.forename: María A
authors.initials: MA
authors.lastname: Fiol-deRoque
authors.affiliation: Laboratory of Molecular Cell Biomedicine, University of the Balearic Islands, Palma, Spain; Lipopharma Therapeutics S.L., Palma, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Torres
authors.affiliation: Laboratory of Molecular Cell Biomedicine, University of the Balearic Islands, Palma, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Ordinas
authors.affiliation: Laboratory of Molecular Cell Biomedicine, University of the Balearic Islands, Palma, Spain; Lipopharma Therapeutics S.L., Palma, Spain.
authors.forename: David J
authors.initials: DJ
authors.lastname: López
authors.affiliation: Laboratory of Genetics, University of the Balearic Islands, Palma de Mallorca, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Castro
authors.affiliation: Laboratory of Molecular Cell Biomedicine, University of the Balearic Islands, Palma, Spain. Electronic address: pablo.escriba@uib.es.
authors.forename: Pablo V
authors.initials: PV
authors.lastname: Escribá
authors.affiliation: Laboratory of Molecular Cell Biomedicine, University of the Balearic Islands, Palma, Spain. Electronic address: xavier.busquets@uib.es.
authors.forename: Xavier
authors.initials: X
authors.lastname: Busquets
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004331:Drosophila melanogaster; D005227:Fatty Acids / Q000032:analysis; D006900:Hydroxylation; D008055:Lipids / Q000032:analysis*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*
chemical_list: D005227:Fatty Acids; D008055:Lipids; D004281:Docosahexaenoic Acids
keywords: Amyloid; Brain lipids; Familial Alzheimer's disease; Omega-3; PUFA; Tau