Sex-specific effects of N-3 PUFA supplementation on brain plasticity in the developing brain

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This research program expands the study of omega-3 polyunsaturated fatty acid (n-3 PUFA) supplemented diets on remodelling of brain function and behavior. Brain development and function is critically dependent on the intake of essential fatty acids that cannot be readily synthesized by the human body. Fish oil is the principal dietary source of the longer-chain n-3 PUFA. Salmon is a rich dietary source, and high-grade pharmaceutical fish oil formulations are also easily available for human consumption. Assessment of the role of n-3 PUFA is an important question considering the growing consumption of processed foods in Western societies, which result in n-3 deficiency and disproportionately high n-6/n-3 PUFA ratio which has been shown to dysregulate brain activity. It is well acknowledged that n-3 PUFA rich diet during gestation promotes neuronal development, and has beneficial effects on cognitive function and neuroplasticity/protection in aged animals or consequent to brain injury. Human studies have reported beneficial effects of n-3 PUFA on cognition and mood in adolescents, which appear different in boys and girls. The adolescent period is a critical period for brain maturation and important remodelling of synapses and reorganization of neurochemical systems characterize this period. Therefore, it is surprising that effects of n-3 PUFA during this developmental stage has not been determined in controlled studies. My research has shown that the adolescent brain is highly sensitive to environmental changes, and expression of important regulators of brain plasticity (Brain-Derived Neurotrophic Factor (BDNF) and its receptor TrkB) is differentially affected by dietary composition and stress exposure in male and female rats. These changes affect key structures of the mesocorticolimbic system, including the nucleus accumbens, amygdala and hippocampus, which regulate cognitive function and emotional responses. Thus, the proposed series of experiments aim to characterize effects of adolescent n-3 PUFA supplementation on cognition and learning-induced plasticity, and determine how sex-specific plastic changes in the mesocorticolimbic system affects biochemical signaling, and memory, social/emotional functions. This research will also determine if dietary omega-3 supplementation can mitigate stress effects experienced as adolescents, and influence cognitive function associated with prefrontal cortex maturation (i.e, decision making and impulsivity). Considering sexually dimorphic hormonal changes in the pubertal period likely to influence bio-behavioural responses, our studies include both males and females, enabling extrapolation of findings to the population as a whole. This research program will foster knowledge of the impact of omega-3 PUFA intake on functional plasticity of distinctive brain systems, examine concomitant behavioural changes, and characterize if benefits of n-3 PUFA consumption in adolescence are perduring in adulthood.