From invertebrates to humans, serotonin (5-HT) exerts structural effects, especially during development. The 5-HT transporter (SERT) directly regulates these effects by maintaining extracellular 5-HT concentrations within a physiological range and possibly by modulating the intracellular redox state of the cell. This chapter addresses 5-HT trophic effects on developing neural and non-neural mammalian cells, and summarizes SERT roles in 5HT-mediated structural effects from basic neurodevelopment to human teratology.
The neurotransmitter serotonin (5-HT) is known to influence behavioral, autonomic, and cognitive functions, including learning and memory, sleep, temperature regulation, appetite, and mood. 5HT also plays a major role in human disorders such as anxiety, fear, depression, obsessive compulsive behavior, autism, and aggression. In addition to triggering a wide variety of electrophysiological effects, 5-HT also exerts important developmental roles in neural and non-neural tissues from early embryogenesis. In many regions of the central nervous system (CNS), this dual “functional” and “structural” involvement is interestingly paralleled at the histological and molecular levels by classical synaptic neurotransmission co-existing with paracrine mechanisms typical of “volume” or “mass” transmission. Indeed, many serotoninergic presynaptic terminals are not in direct proximity to postsynaptic elements. Many 5-HT receptors display CNS distributions necessarily implying the existence of abundant extrasynaptic binding sites, and the 5-HT transporter (SERT) is distributed along 5-HT axonal membranes mostly at extrasynaptic, non-junctional sites.