Similar Datasets
Project description:Serotonergic neurons have multiple roles, including regulating mood and behavior1,2, yet it remains unclear which of these phenotypes are caused by serotonin produced by the central versus the peripheral nervous system. Neuronal serotonin is produced by the enzyme tryptophan hydroxylase 2 (Tph2)3. Mice that lack Tph2 exhibit decreased gut motility4 and several behavioral disorders, including decreased anxiety-like behavior and increased aggression5. To clarify the specific role of peripheral serotonergic circuits, here we engineered mice with intact Tph2 in central neurons but lacking Tph2 in peripheral neurons (Tph2fl/fl; Hand2-Cre). We discovered that PSN contribute to gut motility and are important in the control of anxiety-like behavior but do not contribute to impulsive aggression. Thus, central and peripheral serotonergic neurons have different roles in behavioral regulation. Intriguingly, animals lacking peripheral neuronal Tph2 had deficiencies in enteric immune cells, including reduced abundance of dendritic cells (DC) and IgA+ B cells in the small intestine and elevated susceptibility to oral Salmonella infection. Mechanistic studies suggest that serotonin produced by PSN promotes activation of DC through the 5-HT7 receptor, thereby facilitating DC-mediated differentiation of IgA+ B cells. Our findings highlight the importance of serotonin produced by peripheral neurons for control of behavior and gut defense and suggest that these circuits could be valuable targets for therapeutics.
2024-09-04 | GSE227333 | GEO
Project description:Serotonergic neurons have multiple roles, including regulating mood and behavior1,2, yet it remains unclear which of these phenotypes are caused by serotonin produced by the central versus the peripheral nervous system. Neuronal serotonin is produced by the enzyme tryptophan hydroxylase 2 (Tph2). Mice that lack Tph2 exhibit decreased gut motility4 and several behavioral disorders, including decreased anxiety-like behavior and increased aggression5. To clarify the specific role of peripheral serotonergic circuits, here we engineered mice with intact Tph2 in central neurons but lacking Tph2 in peripheral neurons (Tph2fl/fl; Hand2-Cre). We discovered that PSN contribute to gut motility and are important in the control of anxiety-like behavior but do not contribute to impulsive aggression. Thus, central and peripheral serotonergic neurons have different roles in behavioral regulation. Intriguingly, animals lacking peripheral neuronal Tph2 had deficiencies in enteric immune cells, including reduced abundance of dendritic cells (DC) and IgA+ B cells in the small intestine and elevated susceptibility to oral Salmonella infection. Mechanistic studies suggest that serotonin produced by PSN promotes activation of DC through the 5-HT7 receptor, thereby facilitating DC-mediated differentiation of IgA+ B cells. Our findings highlight the importance of serotonin produced by peripheral neurons for control of behavior and gut defense and suggest that these circuits could be valuable targets for therapeutics.
2024-09-04 | GSE227216 | GEO
Project description:Serotonergic neurons have multiple roles, including regulating mood and behavior1,2, yet it remains unclear which of these phenotypes are caused by serotonin produced by the central versus the peripheral nervous system. Neuronal serotonin is produced by the enzyme tryptophan hydroxylase 2 (Tph2). Mice that lack Tph2 exhibit decreased gut motility4 and several behavioral disorders, including decreased anxiety-like behavior and increased aggression5. To clarify the specific role of peripheral serotonergic circuits, here we engineered mice with intact Tph2 in central neurons but lacking Tph2 in peripheral neurons (Tph2fl/fl; Hand2-Cre). We discovered that PSN contribute to gut motility and are important in the control of anxiety-like behavior but do not contribute to impulsive aggression. Thus, central and peripheral serotonergic neurons have different roles in behavioral regulation. Intriguingly, animals lacking peripheral neuronal Tph2 had deficiencies in enteric immune cells, including reduced abundance of dendritic cells (DC) and IgA+ B cells in the small intestine and elevated susceptibility to oral Salmonella infection. Mechanistic studies suggest that serotonin produced by PSN promotes activation of DC through the 5-HT7 receptor, thereby facilitating DC-mediated differentiation of IgA+ B cells. Our findings highlight the importance of serotonin produced by peripheral neurons for control of behavior and gut defense and suggest that these circuits could be valuable targets for therapeutics.
2024-09-04 | GSE227208 | GEO
Project description:Serotonergic neurons have multiple roles, including regulating mood and behavior1,2, yet it remains unclear which of these phenotypes are caused by serotonin produced by the central versus the peripheral nervous system. Neuronal serotonin is produced by the enzyme tryptophan hydroxylase 2 (Tph2). Mice that lack Tph2 exhibit decreased gut motility4 and several behavioral disorders, including decreased anxiety-like behavior and increased aggression5. To clarify the specific role of peripheral serotonergic circuits, here we engineered mice with intact Tph2 in central neurons but lacking Tph2 in peripheral neurons (Tph2fl/fl; Hand2-Cre). We discovered that PSN contribute to gut motility and are important in the control of anxiety-like behavior but do not contribute to impulsive aggression. Thus, central and peripheral serotonergic neurons have different roles in behavioral regulation. Intriguingly, animals lacking peripheral neuronal Tph2 had deficiencies in enteric immune cells, including reduced abundance of dendritic cells (DC) and IgA+ B cells in the small intestine and elevated susceptibility to oral Salmonella infection. Mechanistic studies suggest that serotonin produced by PSN promotes activation of DC through the 5-HT7 receptor, thereby facilitating DC-mediated differentiation of IgA+ B cells. Our findings highlight the importance of serotonin produced by peripheral neurons for control of behavior and gut defense and suggest that these circuits could be valuable targets for therapeutics.
2024-09-04 | GSE227217 | GEO
Project description:Serotonergic neurons have multiple roles, including regulating mood and behavior1,2, yet it remains unclear which of these phenotypes are caused by serotonin produced by the central versus the peripheral nervous system. Neuronal serotonin is produced by the enzyme tryptophan hydroxylase 2 (Tph2)3. Mice that lack Tph2 exhibit decreased gut motility4 and several behavioral disorders, including decreased anxiety-like behavior and increased aggression5. To clarify the specific role of peripheral serotonergic circuits, here we engineered mice with intact Tph2 in central neurons but lacking Tph2 in peripheral neurons (Tph2fl/fl; Hand2-Cre). We discovered that PSN contribute to gut motility and are important in the control of anxiety-like behavior but do not contribute to impulsive aggression. Thus, central and peripheral serotonergic neurons have different roles in behavioral regulation. Intriguingly, animals lacking peripheral neuronal Tph2 had deficiencies in enteric immune cells, including reduced abundance of dendritic cells (DC) and IgA+ B cells in the small intestine and elevated susceptibility to oral Salmonella infection. Mechanistic studies suggest that serotonin produced by PSN promotes activation of DC through the 5-HT7 receptor, thereby facilitating DC-mediated differentiation of IgA+ B cells. Our findings highlight the importance of serotonin produced by peripheral neurons for control of behavior and gut defense and suggest that these circuits could be valuable targets for therapeutics.
2024-09-04 | GSE227338 | GEO
Project description:Serotonergic neurons have multiple roles, including regulating mood and behavior1,2, yet it remains unclear which of these phenotypes are caused by serotonin produced by the central versus the peripheral nervous system. Neuronal serotonin is produced by the enzyme tryptophan hydroxylase 2 (Tph2). Mice that lack Tph2 exhibit decreased gut motility4 and several behavioral disorders, including decreased anxiety-like behavior and increased aggression5. To clarify the specific role of peripheral serotonergic circuits, here we engineered mice with intact Tph2 in central neurons but lacking Tph2 in peripheral neurons (Tph2fl/fl; Hand2-Cre). We discovered that PSN contribute to gut motility and are important in the control of anxiety-like behavior but do not contribute to impulsive aggression. Thus, central and peripheral serotonergic neurons have different roles in behavioral regulation. Intriguingly, animals lacking peripheral neuronal Tph2 had deficiencies in enteric immune cells, including reduced abundance of dendritic cells (DC) and IgA+ B cells in the small intestine and elevated susceptibility to oral Salmonella infection. Mechanistic studies suggest that serotonin produced by PSN promotes activation of DC through the 5-HT7 receptor, thereby facilitating DC-mediated differentiation of IgA+ B cells. Our findings highlight the importance of serotonin produced by peripheral neurons for control of behavior and gut defense and suggest that these circuits could be valuable targets for therapeutics.
2024-09-04 | GSE227125 | GEO
Project description:Plasmacytoid dendritic cells (pDC) are a specialized sensor of viral and bacterial nucleic acids and a major producer of IFN-? that promotes host defense by priming both innate and acquired immune responses. Although synthetic Toll-like receptor (TLR) ligands, pathogenic bacteria and viruses activate pDC, there is limited investigation of non-pathogenic microbiota that are in wide industrial dietary use, such as lactic acid bacteria (LAB). In this study, we screened for LAB strains, which induce pDC activation and IFN-? production using murine bone marrow (BM)-derived Flt-3L induced dendritic cell culture. Microbial strains with such activity on pDC were absent in a diversity of bacillary strains, but were observed in certain spherical species (Lactococcus, Leuconostoc, Streptococcus and Pediococcus), which was correlated with their capacity for uptake by pDC. Detailed study of Lactococcus lactis subsp. lactis JCM5805 and JCM20101 revealed that the major type I and type III interferons were induced (IFN-?, -?, and ?). IFN-? induction was TLR9 and MyD88-dependent; a slight impairment was also observed in TLR4(-/-) cells. While these responses occurred with purified pDC, IFN-? production was synergistic upon co-culture with myeloid dendritic cells (mDC), an interaction that required direct mDC-pDC contact. L. lactis strains also stimulated expression of immunoregulatory receptors on pDC (ICOS-L and PD-L1), and accordingly augmented pDC induction of CD4(+)CD25(+)FoxP3(+) Treg compared to the Lactobacillus strain. Oral administration of L. lactis JCM5805 induced significant activation of pDC resident in the intestinal draining mesenteric lymph nodes, but not in a remote lymphoid site (spleen). Taken together, certain non-pathogenic spherical LAB in wide dietary use has potent and diverse immunomodulatory effects on pDC potentially relevant to anti-viral immunity and chronic inflammatory disease.
| S-EPMC3323594 | biostudies-literature
Project description:The enteric nervous system (ENS) is crucial for essential gastrointestinal physiologic functions such as motility, fluid secretion, and blood flow. The gut is colonized by trillions of bacteria that regulate host production of several signaling molecules including serotonin (5-HT) and other hormones and neurotransmitters. Approximately 90% of 5-HT originates from the intestine, and activation of the 5-HT4 receptor in the ENS has been linked to adult neurogenesis and neuroprotection. Here, we tested the hypothesis that the gut microbiota could induce maturation of the adult ENS through release of 5-HT and activation of 5-HT4 receptors. Colonization of germ-free mice with a microbiota from conventionally raised mice modified the neuroanatomy of the ENS and increased intestinal transit rates, which was associated with neuronal and mucosal 5-HT production and the proliferation of enteric neuronal progenitors in the adult intestine. Pharmacological modulation of the 5-HT4 receptor, as well as depletion of endogenous 5-HT, identified a mechanistic link between the gut microbiota and maturation of the adult ENS through the release of 5-HT and activation of the 5-HT4 receptor. Taken together, these findings show that the microbiota modulates the anatomy of the adult ENS in a 5-HT-dependent fashion with concomitant changes in intestinal transit.
| S-EPMC6016808 | biostudies-other
Project description:The proglucagon-derived peptide glucagon-like peptide 2 (GLP-2), a product of a subset of gut epithelial cells, is pursued clinically for its ability to stimulate gut epithelial growth and repair. Here we show that although specific epithelial progenitors respond to GLP-2 administration, the epithelium does not express the GLP-2 receptor. Rather, enteric neurons express the receptor, respond to GLP-2, and transmit a signal (which can be blocked by the voltage-gated sodium channel inhibitor tetrodotoxin) back to the epithelium. Thus the nervous system is a key component of a feedback loop regulating epithelial growth and repair.
| S-EPMC60082 | biostudies-literature
Project description:The gut contains a large 5-HT pool in enterochromaffin (EC) cells and a smaller 5-HT pool in the enteric nervous system (ENS). During development, enteric neurons are generated asynchronously. We tested hypotheses that serotonergic neurons, which arise early, affect development/survival of later-born dopaminergic, GABAergic, nitrergic, and calcitonin gene-related peptide-expressing neurons and are essential for gastrointestinal motility. 5-HT biosynthesis depends on tryptophan hydroxylase 1 (TPH1) in EC cells and on TPH2 in neurons; therefore, mice lacking TPH1 and/or TPH2 distinguish EC-derived from neuronal 5-HT. Deletion of TPH2, but not TPH1, decreased myenteric neuronal density and proportions of dopaminergic and GABAergic neurons but did not affect the extrinsic sympathetic innervation of the gut; intestinal transit slowed in mice lacking TPH2 mice, but gastric emptying accelerated. Isolated enteric crest-derived cells (ENCDCs) expressed the serotonin reuptake transporter (SERT) and 15 subtypes of 5-HT receptor. Addition of 5-HT to cultures of isolated ENCDCs promoted total and dopaminergic neuronal development. Rings of SERT-immunoreactive terminal axons surrounded myenteric dopaminergic neurons and SERT knock-out increased intestinal levels of dopamine metabolites, implying that enteric dopaminergic neurons receive a serotonergic innervation. Observations suggest that constitutive gastrointestinal motility depends more on neuronal than EC cell serotonin; moreover, serotonergic neurons promote development/survival of some classes of late-born enteric neurons, including dopaminergic neurons, which appear to innervate and activate in the adult ENS.
| S-EPMC4442094 | biostudies-literature