Topic
TPH1
About: TPH1 is a research topic. Over the lifetime, 268 publications have been published within this topic receiving 14217 citations. The topic is also known as: TPRH & TRPH.
Papers published on a yearly basis
Papers
TL;DR: The neurotransmitter serotonin [5-hydroxytryptamine (5-HT] is causally involved in multiple central nervous facets of mood control and in regulating sleep, anxiety, alcoholism, drug abuse, food intake, and sexual behavior.
Abstract: The neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] is causally involved in multiple central nervous facets of mood control and in regulating sleep, anxiety, alcoholism, drug abuse, food intake, and sexual behavior ([1][1]). In peripheral tissues, 5-HT regulates vascular tone, gut motility,
1,617 citations
TL;DR: Gut microbiota acting through SCFAs are important determinants of enteric 5‐HT production and homeostasis through an effect of short‐chain fatty acids on enterochromaffin cells.
Abstract: Gut microbiota alterations have been described in several diseases with altered gastrointestinal (GI) motility, and awareness is increasing regarding the role of the gut microbiome in modulating GI function. Serotonin [5-hydroxytryptamine (5-HT)] is a key regulator of GI motility and secretion. To determine the relationship among gut microbes, colonic contractility, and host serotonergic gene expression, we evaluated mice that were germ-free (GF) or humanized (HM; ex-GF colonized with human gut microbiota). 5-HT reduced contractile duration in both GF and HM colons. Microbiota from HM and conventionally raised (CR) mice significantly increased colonic mRNAs Tph1 [(tryptophan hydroxylase) 1, rate limiting for mucosal 5-HT synthesis; P < 0.01] and chromogranin A (neuroendocrine secretion; P < 0.01), with no effect on monoamine oxidase A (serotonin catabolism), serotonin receptor 5-HT4, or mouse serotonin transporter. HM and CR mice also had increased colonic Tph1 protein (P < 0.05) and 5-HT concentrations (GF, 17 ± 3 ng/mg; HM, 25 ± 2 ng/mg; and CR, 35 ± 3 ng/mg; P < 0.05). Enterochromaffin (EC) cell numbers (cells producing 5-HT) were unchanged. Short-chain fatty acids (SCFAs) promoted TPH1 transcription in BON cells (human EC cell model). Thus, gut microbiota acting through SCFAs are important determinants of enteric 5-HT production and homeostasis.
1,062 citations
TL;DR: It is shown here that Lrp5 inhibits expression of Tph1, the rate-limiting biosynthetic enzyme for serotonin in enterochromaffin cells of the duodenum, and decreasing serotonin blood levels normalizes bone formation and bone mass in L rp5-deficient mice.
837 citations
TL;DR: There are two serotonin systems in vertebrates, independently regulated and with distinct functions, and these findings clarify puzzling data, which have been collected over the last decades about partially purified TPH proteins with different characteristics and justify a new concept of the serotonin system.
771 citations
TL;DR: This work reports a functional (C1473G) single-nucleotide polymorphism in mouse Tph2 that results in the substitution of Pro447 with Arg447 and leads to decreased serotonin levels in PC12 cells, providing direct evidence for a fundamental role of Tph1 in brain serotonin synthesis.
Abstract: Dysregulation of brain serotonin contributes to many psychiatric disorders. Tryptophan hydroxylase-2 (Tph2), rather than Tph1, is preferentially expressed in the brain. We report a functional (C1473G) single-nucleotide polymorphism in mouse Tph2 that results in the substitution of Pro447 with Arg447 and leads to decreased serotonin levels in PC12 cells. Moreover, in BALB/cJ and DBA/2 mice that are homozygous for the 1473G allele, brain serotonin tissue content and synthesis are reduced in comparison to C57Bl/6 and 129X1/SvJ mice that are homozygous for the 1473C allele. Our data provide direct evidence for a fundamental role of Tph2 in brain serotonin synthesis.
715 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 21 |
| 2020 | 23 |
| 2019 | 14 |
| 2018 | 11 |
| 2017 | 20 |
| 2016 | 9 |