Role of Production and Degradation of Serotonin During Development

ABSTRACT

Serotonin (5-hydroxytryptamine [5-HT]) is one of the major neurotransmitter in the brain. Since 5-HT is carried by 5-HT transporters and the biological activities of 5-HT are exerted through 5-HT receptors, disturbed regulation of 5-HT transporters and receptors in the adult brain has been implicated in pathological conditions in central nervous systems. On the other hand, proper 5-HT neurotransmission during development underlies the mature functional architecture of serotonergic neurons, and an increasing body of evidence suggests the involvement of developmental brain disturbances in psychiatric disorders. Genetic mouse models have shown that 5-HT receptors and the 5-HT transporter acting during developmental stages modulate developmental processes. In addition, recent works demonstrated that appropriate 5-HT production and 5-HT degradation during develoment are needed for the development of 5-HT neurons and brain functions in the adult. In this review article, we focus on the importance of activities of tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT biosynthesis and monoamine oxidase A (MAOA), a catabolic enzyme responsible for degradation of 5-HT during development for the brain functions in the adult.