Gender differences in rat erythrocyte and brain docosahexaenoic acid composition: Role of ovarian hormones and dietary omega-3 fatty acid composition

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 mate and female rats, and in chronically ovariectomized (OVX) rats with or without cyclic estradiol treatment (2 mu g/4 d). All groups were maintained on diets with or without the DHA precursor alpha-linolenic acid (ALA, 18:3n-3). We report that both mate (-21%) and OVX (-19%) rats on ALA+ diet exhibited significantly lower erythrocyte DHA composition relative to female controls. Females on ALA+ diet exhibited tower DHA composition in the prefrontal cortex (PFC) relative mates (-5%). OVX rats on ALA+ diet exhibited significantly tower 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 tower erythrocyte and regional brain DHA composition relative to groups on ALA+ diet, and these reductions were greater in mates but not in OVX rats. These preclinical data corroborate clinical evidence for gender differences in peripheral DHA composition (female > mate), demonstrate gender differences in PFC DHA composition (mate > female), and support a link between ovarian hormones and erythrocyte and region-specific brain DHA composition. (C) 2008 Elsevier Ltd. All rights reserved.