title: Hippocampal Lipid Homeostasis in APP/PS1 Mice is Modulated by a Complex Interplay Between Dietary DHA and Estrogens: Relevance for Alzheimer's Disease.
abstract: Current evidence suggests that lipid homeostasis in the hippocampus is affected by different genetic, dietary, and hormonal factors, and that its deregulation may be associated with the onset and progression of Alzheimer's disease (AD). However, the precise levels of influence of each of these factors and their potential interactions remain largely unknown, particularly during neurodegenerative processes. In the present study, we have performed multifactorial analyses of the combined effects of diets containing different doses of docosahexaenoic acid (DHA), estrogen status (ovariectomized animals receiving vehicle or 17β-estradiol), and genotype (wild-type or transgenic APP/PS1 mice) in hippocampal lipid profiles. We have observed that the three factors affect lipid classes and fatty acid composition to different extents, and that strong interactions between these factors exist. The most aberrant lipid profiles were observed in APP/PS1 animals receiving DHA-poor diets and deprived of estrogens. Conversely, wild-type animals under a high-DHA diet and receiving estradiol exhibited a lipid profile that closely resembled that of the hippocampus of control animals. Interestingly, though the lipid signatures of APP/PS1 hippocampi markedly differed from wild-type, administration of a high-DHA diet in the presence of estrogens gave rise to a lipid profile that approached that of control animals. Paralleling changes in lipid composition, patterns of gene expression of enzymes involved in lipid biosynthesis were also altered and affected by combination of experimental factors. Overall, these results indicate that hippocampal lipid homeostasis is strongly affected by hormonal and dietary conditions, and that manipulation of these factors might be incorporated in AD therapeutics.
authors.affiliation: Department of Animal Physiology, Laboratory of Membrane Physiology and Biophysics, University of La Laguna, Tenerife, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Díaz
authors.affiliation: Department of Animal Physiology, Laboratory of Membrane Physiology and Biophysics, University of La Laguna, Tenerife, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Fabelo
authors.affiliation: Department of Genetics, University of La Laguna, Tenerife, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Casañas-Sánchez
authors.affiliation: Department of Physiology, Laboratory of Cellular Neurobiology, University of La Laguna, Tenerife, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Marin
authors.affiliation: Department of Animal Physiology, Laboratory of Membrane Physiology and Biophysics, University of La Laguna, Tenerife, Spain.
authors.forename: Tomás
authors.initials: T
authors.lastname: Gómez
authors.affiliation: Department of Animal Physiology, Laboratory of Membrane Physiology and Biophysics, University of La Laguna, Tenerife, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Quinto-Alemany
authors.affiliation: Department of Genetics, University of La Laguna, Tenerife, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Pérez
mesh_terms: D000214:Acyl Coenzyme A / Q000235:genetics / Q000378:metabolism; D000544:Alzheimer Disease / Q000178:diet therapy / Q000235:genetics / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000214:Acyl Coenzyme A; D016564:Amyloid beta-Protein Precursor; D004967:Estrogens; D053764:Presenilin-1; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids
keywords: 17β-estradiol; Alzheimer’s disease; docosahexaenoic acid; hippocampal lipids; multifactor analyses