Food and metabolic signalling defects in a Caenorhabditis elegans serotonin-synthesis mutant

Abstract

The functions of serotonin have been assigned through serotonin-receptor-specific drugs and mutants; however, because a constellation of receptors remains when a single receptor subtype is inhibited, the coordinate responses to modulation of serotonin levels may be missed. Here we report the analysis of behavioural and neuroendocrine defects caused by a complete lack of serotonin signalling. Analysis of the C. elegans genome sequence showed that there is a single tryptophan hydroxylase gene (tph-1)-the key enzyme for serotonin biosynthesis. Animals bearing a tph-1 deletion mutation do not synthesize serotonin but are fully viable. The tph-1 mutant shows abnormalities in behaviour and metabolism that are normally coupled with the sensation and ingestion of food: rates of feeding and egg laying are decreased; large amounts of fat are stored; reproductive lifespan is increased; and some animals arrest at the metabolically inactive dauer stage. This metabolic dysregulation is, in part, due to downregulation of transforming growth factor-beta and insulin-like neuroendocrine signals. The action of the C. elegans serotonergic system in metabolic control is similar to mammalian serotonergic input to metabolism and obesity.

Fishing lines, time‐delayed guideposts, and other tricks used by developing pharyngeal neurons in Caenorhabditis elegans

“…The thin process may serve a sensory function that monitors the state of the pharyngeal lumen. The NSM neurons can secrete serotonin (Horvitz et al, 1982;Sze et al, 2000), glutamate (Lee et al, 1999), and the neuropeptide-like proteins NLP-13, NLP-18, and NLP-19 (Nathoo et al, 2001). Given their trajectories and connectivity, the NSM neurons are likely able to convey information about the presence of food in the pharynx to the rest of the worm, thus affecting foraging behavior.…”

“…They project in opposite directions, differ in their circumferential trajectories (NSM projects in the pharyngeal nerve ring while M2 projects anterior through it, piercing a path through he pm4 cell), and NSM but not M2 is branched. They also offer relatively simple shapes that facilitate scoring of deviant forms, and, importantly, useful green fluorescent protein (GFP) reporters are available for their visualization: pRIC-19::GFP for the M2 neurons (Pilon et al, 2000), and pTPH-1::GFP for the NSM neurons (Sze et al, 2000).…”

Dissecting a central flip-flop circuit that integrates contradictory sensory cues in C. elegans feeding regulation

“…The neurotransmitter 5-hydroxytryptamine (5-HT, serotonin) regulates food-related behaviours and physiology in diverse vertebrate and invertebrate phyla [15][16][17][18] . It is known that 5-HT increases pumping rate in the absence of food 19 , while tph-1 mutants, which fail to synthesize 5-HT, display reduced feeding 17 . In the presence of food, it has been reported that exogenous 5-HT (13 mM) did not stimulate pumping 20 .…”

“…2a,b), suggesting the involvement of 5-HT in sensory-mediated feeding facilitation. In hermaphrodite C. elegans, tph-1 expression is limited to only a few serotonergic neurons, such as NSM, ADF and HSN 17,22 . To locate the release site of 5-HT, we used neuron-specific promoters to drive the expression of TPH-1 in tph-1 mutants.…”

Satiety and amino-acid profile in overweight women after a new treatment using a natural plant extract sublingual spray formulation

“…[8][9][10] Evidence suggesting that defects in the serotonin system may be etiologic of obesity has been also accumulated. 11,12 The synthesis of serotonin in the brain is controlled in part by the availability of its amino-acid precursor, L-tryptophan. Tryptophan pools in the brain are, in turn, influenced by the uptake of tryptophan from the circulation.…”