Tph2 Gene Expression Defines Ethanol Drinking Behavior in Mice

Zaniewska, Magdalena; Mosienko, Valentina; Bäder, Michael; Alenina, Natalia

doi:10.3390/cells11050874

Cited by 9 publications

(2 citation statements)

References 82 publications

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“…Serotonin was associated with ethanol consumption and addiction [94]. Genetic deficiency of TPH2 in mice promotes increased ethanol consumption associated with an ethanol antidepressant phenotype (shorter immobility time in the forced swim test) [95]. Low tryptophan availability has been linked to alcohol dependence [94].…”

Section: Genetics Epigenetics and Tryptophan Metabolismmentioning

confidence: 99%

Tryptophan Metabolism in Developmental Origins of Health and Disease (DOHaD)

Souza,

Silva,

Gomes

et al. 2024

Preprint

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Tryptophan, an essential amino acid in mammals obtained from the diet, is influenced by maternal diet, which impacts early life and development of offspring. This is studied under the Developmental Origins of Diseases and Health (DOHaD) concept, so factors from conception to early childhood affect health and disease susceptibility. Tryptophan is metabolized mainly through two pathways: serotonin (5-HT) and kynurenine. The kynurenine pathway, active in the brain, gut, liver, and placenta, breaks down over 95% of tryptophan and plays roles in inflammation, neurotransmission, immune responses, and immune modulation during pregnancy. The serotonin pathway uses up to 5% of Tryptophan, mainly in the gut, adipose tissues, pancreatic cells, and central nervous system, and regulates responses to environmental changes, including sleep, cognition, and feeding behavior. Key enzymes in these pathways include Trp-2,3-dioxygenase (TDO), indoleamine-2,3-dioxygenase (IDO) type1 (IDO1), and type 2 (IDO2) (kynurenine pathway), and tryptophan hydroxylase type 1 (TPH1) and type 2 (TPH2), serotonin pathway. The fetus-placental unit manages tryptophan metabolism. Serotonin and kynurenine are crucial for placental health and fetal development. Serotonin adjusts placental blood volume and aids neurodevelopment. Kynurenine metabolites protect the fetus from maternal immunity and offer initial neuroprotection. At birth, infants switch from placental nutrients to breast milk, rich in tryptophan and protective bioactive molecules. Tryptophan, solely from breast milk, is crucial for infants. Its levels are high in newborns (first three weeks, 2-4 times higher than in adults), gradually declining to adult levels by the fourth week. The highlights the importance of tryptophan for the serotonin and kynurenine pathways in fetuses, newborns and babies applied to the DOHaD concept.

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Section: Genetics Epigenetics and Tryptophan Metabolismmentioning

confidence: 99%

Tryptophan Metabolism in Developmental Origins of Health and Disease (DOHaD)

Souza,

Silva,

Gomes

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…5-HT has been also found to control segmental motor patterns in small intestine. A study performed in tryptophan hydroxylase deficient (Tph2-/- mice) mice demonstrated the functional aspects of 5-HT in GI motility mainly by attributing with significant reductions in contractile complexes and synaptic transmission due to lower level of 5-HT[ 108 , 109 ]. This is further indicative for the significance of serotonergic neurons, comparing to EC cells for constitutive GI motility.…”

Section: Intestinal Microbiome and Serotonergic Signallingmentioning

confidence: 99%

Molecular signalling during cross talk between gut brain axis regulation and progression of irritable bowel syndrome: A comprehensive review

Singh¹,

Ganguly²,

Jaiswal³

et al. 2023

World J Clin Cases

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Irritable bowel syndrome (IBS) is a chronic functional disorder which alters gastrointestinal (GI) functions, thus leading to compromised health status. Pathophysiology of IBS is not fully understood, whereas abnormal gut brain axis (GBA) has been identified as a major etiological factor. Recent studies are suggestive for visceral hyper-sensitivity, altered gut motility and dysfunctional autonomous nervous system as the main clinical abnormalities in IBS patients. Bidirectional signalling interactions among these abnormalities are derived through various exogenous and endogenous factors, such as microbiota population and diversity, microbial metabolites, dietary uptake, and psychological abnormalities. Strategic efforts focused to study these interactions including probiotics, antibiotics and fecal transplantations in normal and germ-free animals are clearly suggestive for the pivotal role of gut microbiota in IBS etiology. Additionally, neurotransmitters act as communication tools between enteric microbiota and brain functions, where serotonin (5-hydroxytryptamine) plays a key role in pathophysiology of IBS. It regulates GI motility, pain sense and inflammatory responses particular to mucosal and brain activity. In the absence of a better understanding of various interconnected crosstalks in GBA, more scientific efforts are required in the search of novel and targeted therapies for the management of IBS. In this review, we have summarized the gut microbial composition, interconnected signalling pathways and their regulators, available therapeutics, and the gaps needed to fill for a better management of IBS.

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