title: Gender differences in rat erythrocyte and brain docosahexaenoic acid composition: role of ovarian hormones and dietary omega-3 fatty acid composition.
abstract: The two-fold higher prevalence rate of major depression in females may involve vulnerability to omega-3 fatty acid deficiency secondary to a dysregulation in ovarian hormones. However, the role of ovarian hormones in the regulation of brain omega-3 fatty acid composition has not been directly evaluated. Here we determined erythrocyte and regional brain docosahexaenoic acid (DHA, 22:6n-3) composition in intact male and female rats, and in chronically ovariectomized (OVX) rats with or without cyclic estradiol treatment (2 microg/4d). All groups were maintained on diets with or without the DHA precursor alpha-linolenic acid (ALA, 18:3n-3). We report that both male (-21%) and OVX (-19%) rats on ALA+ diet exhibited significantly lower erythrocyte DHA composition relative to female controls. Females on ALA+ diet exhibited lower DHA composition in the prefrontal cortex (PFC) relative males (-5%). OVX rats on ALA+ diet exhibited significantly lower DHA composition in the hippocampus (-6%), but not in the PFC, hypothalamus, or midbrain. Lower erythrocyte and hippocampus DHA composition in OVX rats was not prevented by estrogen replacement. All groups maintained on ALA- diet exhibited significantly lower erythrocyte and regional brain DHA composition relative to groups on ALA+ diet, and these reductions were greater in males but not in OVX rats. These preclinical data corroborate clinical evidence for gender differences in peripheral DHA composition (female>male), demonstrate gender differences in PFC DHA composition (male>female), and support a link between ovarian hormones and erythrocyte and region-specific brain DHA composition.
authors.affiliation: Department of Psychiatry, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0516, United States. robert.mcnamara@psychiatry.uc.edu
authors.forename: Robert K
authors.initials: RK
authors.lastname: McNamara
authors.forename: Jessica
authors.initials: J
authors.lastname: Able
authors.forename: Ronald
authors.initials: R
authors.lastname: Jandacek
authors.forename: Therese
authors.initials: T
authors.lastname: Rider
authors.forename: Patrick
authors.initials: P
authors.lastname: Tso
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004041:Dietary Fats / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D004958:Estradiol / Q000502:physiology*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000378:metabolism; D010052:Ovariectomy; D010053:Ovary; D017397:Prefrontal Cortex / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D020318:Rats, Long-Evans; D012044:Regression Analysis; D012737:Sex Factors
chemical_list: D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; D004958:Estradiol