The Impact of Membrane Polyunsaturated Fatty Acid Composition on Neuronal Growth and Development

PUFAs serve many important biological and physiological functions within the body and are key for the structure and function of the brain. Omega-6 and omega-3 PUFAs are found in abundance in phospholipids of neuronal membranes that impart structure and function of neurons. Omega-6 PUFAs are instrumental for neurotransmission, neuronal elongation, and neuritogenesis; whereas, omega-3 PUFAs promote neuronal maturation through synaptogenesis. The types of PUFAs incorporated into neuronal membranes is especially important in determining the progression of development. The processes of neurogenesis, neuritogenesis and elongation require large amounts of PUFAs to be incorporated into the membrane phospholipids. To accommodate for the high PUFA needs, maternal dietary PUFA, especially EPA and DHA, recommendations, mobilization of fatty acids into maternal circulation increases, and the accretion rate of PUFA are increased. If maternal nutritional inadequacy of PUFAs occurs during gestation, this can result in impaired cognition, behavioral abnormalities, reduced number of neurons, decreased dendric arborization, altered myelin sheath, and a reduction in brain size. Even though the essentiality of PUFAs in neuronal development is widely accepted, the mechanism is not well understood. There is a lack of consensus in the current literature on the effects of individual PUFAs on each stage of neuronal development and the molecular pathways involved. Despite the inconsistent evidence, the results of numerous studies have consistently suggested that neuronal membrane PUFA composition is associated with neuronal development outcomes, such as number of neurons and neurites, neurite length, and neurotransmitter release. The varying results may be the result of methodological discrepancies with PUFA composition and concentrations, as well as the models used for neuronal development. Additionally, very few studies have taken into consideration the competitive relationship of omega-6 and omega-3 PUFAs in the body when assessing neurodevelopment. This thesis was focused on addressing the role of PUFAs in neuronal development and to address some of the inconsistencies in the literature. attempt to elucidate the individual roles of ALA, ARA, and EPA on neuronal membrane composition and neuronal development. The aim of the thesis research project was to assess the impact of individual PUFAs on neuronal membrane PUFA composition, the membrane n-6:n-3 ratio, and the morphology of SH-SY5Y cells during differentiation. The results of this study demonstrated that supplementation of individual PUFAs alters membrane PUFA composition and the n-6:n-3 ratio. However, there wasn’t a significant effect on neurite number with ALA, ARA, and EPA treatment. Lastly, ARA treatment decreased cell viability compared to the other treatments and the BSA control. Furthermore, additional research needs to be conducted to address other morphological measures and functional outcomes, such as neurotransmitter production and release