Polyunsaturated Fatty Acids and their Metabolites in Neural Development and Implications for Psychiatric Disorders

Nobuyuki      Sakayori; Noriko      Osumi

Abstract

n-6 and n-3 polyunsaturated fatty acids (PUFAs) are essential dietary nutrients because they constitute part of the cell membrane, are a source of energy, and function as signaling molecules. Metabolites of PUFAs are strong lipid mediators and play a role in regulating inflammation. PUFAs are transported by specific proteins, and PUFAs and their metabolites act by binding to receptors. These transporter proteins and receptors are encoded by lipid-related genes. The neural system originates from neural stem/progenitor cells (NSPCs). NSPCs first proliferate, increasing their numbers, and then produce the neurons and glial cells that compose the complex neural circuits within the brain. Recently, our group and other groups have shown that PUFAs, their metabolites and lipid-related genes all affect the proliferation and differentiation of embryonic NSPCs, and these fatty acid signaling molecules are involved in neural development. Proper neural development is important for normal function of the adult brain, and impaired neuronal circuit formation causes long-lasting dysfunction. It is now widely accepted that impaired neural development increases an individual’s susceptibility to the onset of psychiatric disorders (a concept known as the “neurodevelopmental theory”). Recent reports show evidence of an association between lipid-related genes and psychiatric disorders. In addition, PUFAs have been reported to have an ameliorative effect on various psychiatric disorders. A better understanding of neurodevelopmental regulation by PUFAs and their metabolites, as well as of the effects of PUFAs on psychiatric disorders, may provide important insight into the relationship between neural development and psychiatric disorders.

Keywords: Arachidonic acid, docosahexaenoic acid, fatty acid, lipid mediator, neural stem cells, neural development, psychiatric disorder, neurodevelopmental theory