Life without Peripheral Serotonin: Insights from Tryptophan Hydroxylase 1 Knockout Mice Reveal the Existence of Paracrine/Autocrine Serotonergic Networks

Abstract

Since its identification, 75 years ago, the monoamine serotonin (5-HT) has attracted considerable attention toward its role as a neurotransmitter in the central nervous system. Yet, increasing evidence, from a growing number of research groups, substantiates the fact that 5-HT regulates important nonneuronal functions. Peripheral 5-HT, synthesized by the enzyme tryptophan hydroxyase (Tph) in intestinal cells, was assumed to be distributed throughout the entire body by blood platelets and to behave as a pleiotropic hormone. A decade ago, generation of a mouse model devoid of peripheral 5-HT lead to the discovery of a second isoform of the enzyme Tph and also suggested that 5-HT might act as a local regulator in various organs. The objective of this review is to highlight the newly discovered functions played by the monoamine using the Tph1 KO murine model and to outline current findings that led to the discovery of complete serotonergic systems in unexpected organs. Within an organ, both the presence of local Tph enzymatic activity and serotonergic components are of particular importance as they support the view that 5-HT meets the criteria to be qualified as a monoamine with a paracrine/autocrine function.

Impact of Maternal Serotonin Transporter Genotype on Placental Serotonin, Fetal Forebrain Serotonin, and Neurodevelopment

“…Serotonin production in the placenta does not appear to account for the maternal genotype effect, as neither tryptophan hydroxylase mRNA expression nor tryptophan hydroxylase activity were altered (Amireault et al, 2013). Within the placenta, SERT is present in the labrynth zone, where cells are of fetal origin, and this expression reaches high levels only later in development (~E17.5; Wu et al, 2016).…”

Increasing serotonin concentrations alter calcium and energy metabolism in dairy cows

“…Serotonin's role as a neurotransmitter in the CNS and its participation in a variety of behavioral functions has been largely documented (Lucki 1998). However, the significance of nonneuronal serotonin is not thoroughly appreciated, despite numerous studies having been conducted on serotonin in a variety of tissues and physiological states (Berger et al 2009, Amireault et al 2013. Only a small percentage (w5%) of the body's total serotonin is found in the CNS, with the majority (w95%) being stored in the platelets and being derived from variety of tissues outside of the CNS (Berger et al 2009).…”

A novel serotonin-secreting cell type regulates ciliary motility in the mucociliary epidermis of Xenopus tadpoles

“…Tryptophan hydroxylase, the rate-limiting enzyme for serotonin synthesis, is encoded by two closely related genes, TPH1/2, which display cell-type-specific expression in non-neural and neural cells, respectively. Serotonin synthesis from 5-hydroxytryptophan is catalyzed by DOPA-decarboxylase (aromatic L-amino acid decarboxylase) (Amireault et al, 2013;Gutknecht et al, 2009). In humans, a number of serotonin-dependent diseases have been described: for example, pulmonary-atrial hypertonia (Berger et al, 2009), irritable bowel syndrome (Mawe et al, 2006) and mental mood disorders such as depression (Berger et al, 2009).…”