Omega‐3 Polyunsaturated Fatty Acids have Sex‐specific Effects on the Phospholipid Fatty Acid Composition and Neurotrophin Expression in the Brain of C57BL/6 Mice

Abstract

Increasing the consumption of docosahexaenoic acid (DHA) causes a greater accretion of DHA in the cortex, which is associated with improved cognition. We have shown that omega (n)‐3 polyunsaturated fatty acids (PUFA) alter the expression of neurotrophins, such as brain‐derived neurotrophic factor and nerve growth factor, which regulates proper cortical function. Different regions of the brain carry out different functions; however, it is not known whether a diet high in n‐3 PUFA causes accretion of DHA in different brain regions, with sex and age‐specificity. We fed female C57BL/6 mice semi‐purified diets (20% fat w/w) either high (10% w/w) or low (2% w/w) in n‐3 PUFA before pregnancy, during gestation, and lactation. Male and female offspring were studied at weaning, or continued on their mother's diet for an additional 16 weeks. Brain cortex, cerebellum and brainstem were collected for phospholipid fatty acid analysis and gene expression. Regardless of diet, females at weaning had lower DHA in the brainstem and cerebellum compared to the males at weaning (P<0.0001). In addition, females at weaning had lower DHA in only the cerebellum compared to females at 16 weeks (p<0.0001). DHA was not different in both sexes at 16 weeks in the cerebellum and brainstem; however the levels decreased significantly with age in the male brainstem (P<0.0001). High n‐3 PUFA diet caused accretion of cortical DHA in both sexes at 16 weeks (P < 0.05). It is being investigated whether alterations in the fatty acid composition have an effect on the gene expression of neurotrophins in various regions of the brain. We are the first to show sex and age‐specific accretion of n‐3 PUFA in various brain regions. Supported by NSERC.