The expression of neurotrophins is differentially regulated by omega-3 polyunsaturated fatty acids at weaning and postweaning in C57BL/6 mice cerebral cortex

• An age dependent effect of omega-3 PUFA on neurotrophin signaling is proposed.
• The accretion of DHA in the cortical phospholipid is affected by diet and age.
• High cortical accretion of DHA upregulates mRNA expressions of key neurotrophins.
• High n-3 PUFA increases the concentration of phosphorylated CREB.
• Accretion of DHA in the brain is vital for neuroprotection and enhanced cognition.

Omega-3 (n-3) polyunsaturated fatty acids (PUFA) and neurotrophins are pivotal to the proper functioning of the central nervous system. We investigated the effects of perinatal and postweaning n-3 PUFA diets on cerebral cortical phospholipid fatty acid composition, and the expression of neurotrophins at weaning and 16 weeks postweaning of the male offspring of C57BL/6 mice. Female C57BL/6 mice were fed semi-purified diets (20% w/w fat) containing 10% (high) and 2% (low) n-3 PUFA before mating, during pregnancy, and until weaning. Offspring were studied at weaning and 16 weeks postweaning on their mother’s designated diet. Cerebral cortical phospholipid fatty acids and mRNA expressions of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), cAMP response element binding protein (CREB), and TrkB were measured. The protein concentration of phosphorylated CREB (pCREB) was determined by ELISA. DHA and total n-3 PUFA were significantly higher in cortical phospholipids of the high n-3 PUFA group compared to the low n-3 PUFA group (P < 0.0001), and increased significantly from weaning to 16 weeks (P < 0.0001). There was a significant effect of diet (P < 0.05) and age (P < 0.05) on the mRNA expression of NGF. The mRNA expression of BDNF increased significantly (P < 0.01) in the high n-3 PUFA group compared to the low n-3 PUFA group. The mRNA expression of TrKB was significantly higher (P < 0.0001) at 16 weeks in the high n-3 PUFA group compared to the low n-3 PUFA group; however, no difference was observed at weaning. pCREB/Total CREB was higher in the high n-3 PUFA group compared to the low n-3 PUFA group (P < 0.05). Our findings demonstrate that perinatal and postweaning diets high in n-3 PUFA lead to accretion of n-3 PUFA in brain cortex. We further found that n-3 PUFA upregulates the expression of neurotrophins and their target receptors in an age dependent fashion.