The Intricate Biological Proximity of Vitamin D and Brain Serotonin

Background: The purpose of this article is to extend and elaborate on our current understanding of Calcitriol and Brain Serotonin synthesis; particularly on how the two may be related. Methods: Using a 2014 study involving clinical trials to extend this hypothesis. Results: Vitamin D (Calcitriol) activated the gene that codes for Tryptophan Hydroxylase 2, which synthesizes Brain Serotonin. It also inhibits Tryptophan Hydroxylase 1, which makes serotonin in the gut. Conclusion: Vitamin D is closely related to the synthesis of Brain Serotonin. If furthered, it may be used as a treatment for the Serotonin Anomaly in Autistic Children. Keywords: 1. Biochemistry 2. Genetics 3. Neuroscience 4. Physiology

Is sleep bruxism related to the levels of enzymes involved in the serotonin synthesis pathway?

Objectives This exploratory research aimed to evaluate the levels of tryptophan hydroxylase 1 (TPH1) and aromatic l-amino acid decarboxylase (DDC), which play an important role in the serotonin synthesis pathway, in individuals with sleep bruxism (SB) diagnosed using audio–video polysomnography (vPSG) and compare them with that of individuals not presenting with SB. Materials and methods The study included adult patients hospitalized in the Department and Clinic of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology at the Wroclaw Medical University. The participants underwent a single-night vPSG for the evaluation of the SB parameters. Peripheral blood samples were also collected from them for estimating the serum levels of TPH1 and DDC. Results A total of 105 patients (80 women and 25 men) were included in the study. All the patients were Caucasians and aged 18–63 years (mean age: 33.43 ± 10.8 years). Seventy-five patients (71.43%) presented with SB, of which 50 (47.62%) had severe SB, while the remaining 30 patients (28.57%) did not. No statistically significant differences in TPH1 and DDC levels were observed between the individuals with SB and without SB. A significant negative correlation was found between tonic SB episodes and DDC levels (p = 0.0012). Other correlations between the SB parameters and the levels of the studied enzymes were statistically insignificant (p > 0.05 for all comparisons). Conclusions The levels of the enzymes that are crucial for serotonin synthesis (TPH1 and DDC) did not seem to influence SB. Clinical relevance This study provides important insights for further research on the relationship between the serotonin pathway and SB, which should take into account not only the process of serotonin synthesis but also the effect of serotonin-dependent neurotransmission on SB.

Treating Depression and other Serotonin Deficiency Brain Disorders with Tryptophan

: Deficits of brain serotonin (5-hydroxytryptamine; 5-HT) are implicated in a number of psychiatric illnesses including depression. Treatment efficacy of this highly prevalent brain disorder is not adequate largely because serotonin stores are depleted. Tryptophan an essential amino acid is the sole precursor of serotonin; its systemic or oral administration increases serotonin synthesis because tryptophan hydroxylase, the rate limiting enzyme of 5-HT biosynthesis, is physiologically unsaturated with its substrate. The present article targets importance of tryptophan supplementation in treating serotonin deficiency and improving therapeutic intervention in depression and other serotonin deficiency brain disorders.

TPH1 gene polymorphism rs211105 is associated with serotonin and tryptophan hydroxylase 1 concentrations in acute pancreatitis patients

Background The role of serotonin and its metabolic pathway in proper functioning of the pancreas has not been thoroughly investigated yet in acute pancreatitis (AP) patients. Tryptophan hydroxylase (TPH) as the rate-limiting enzyme of serotonin synthesis has been considered for possible associations in various diseases. Single-nucleotide polymorphisms (SNPs) in TPH genes have been already described in associations with psychiatric and digestive system disorders. This study aimed to explore the association of a rs211105 (T/G) polymorphism in TPH1 gene with tryptophan hydroxylase 1 concentrations in blood serum in a population of acute pancreatitis patients, and to investigate this association with acute pancreatitis susceptibility. Results Our data showed an association between the presence of the T allele at the position rs211105 (OR = 2.47, 95 % CI 0.94–6.50, p = 0.06) under conditions of a decreased AP incidence. For TT and GT genotypes in the control group, the lowest concentration of TPH was associated with higher serotonin levels (TT: Rs = − 0.415, p = 0.0018; GT: Rs = − 0.457, p = 0.0066), while for the AP group the highest levels of TPH among the TT genotype were associated with lower levels of serotonin (TT: Rs = − 0.749, p < 0.0001, and in the GG genotype higher levels of TPH were associated with higher levels of serotonin (GG: Rs = − 0.738, p = 0.037). Conclusions Here, a new insight in the potential role of a selected genetic factor in pancreatitis development was shown. Not only the metabolic pathway of serotonin, but also factors affecting serotonin synthesis may be interesting and important points in acute pancreatitis.

TPH1 gene polymorphism rs211105 influences serotonin and tryptophan hydroxylase 1 concentrations in acute pancreatitis patients

Background The role of serotonin and its metabolic pathway in proper functioning of the pancreas has not been thoroughly investigated yet in acute pancreatitis (AP) patients. Tryptophan hydroxylase (TPH) as the rate-limiting enzyme of serotonin synthesis has been considered for possible associations in various diseases. Single-nucleotide polymorphisms (SNPs) in TPH genes have been already described in associations with psychiatric and digestive system disorders. This study aimed to explore the association of a rs211105 (T/G) polymorphism in TPH1 gene with tryptophan hydroxylase 1 concentrations in blood serum in a population of acute pancreatitis patients, and to investigate this association with acute pancreatitis susceptibility. Results Our data showed an association between the presence of the T allele at the position rs211105 (OR = 2.47, 95% CI: 0.94-6.50, p = 0.06) under conditions of a decreased AP incidence. For TT and GT genotypes in the control group, the lowest concentration of TPH was associated with higher serotonin levels (TT: Rs=-0.415, p=0.0018; GT: Rs=-0,457, p=0.0066), while for the AP group the highest levels of TPH among the TT genotype were associated with lower levels of serotonin (TT: Rs=-0.749, p<0.0001, and in the GG genotype higher levels of TPH were associated with higher levels of serotonin (GG: Rs=-0.738, p=0.037). Conclusions Here, a new insight in the potential role of a selected genetic factor in pancreatitis development was shown. Not only the metabolic pathway of serotonin, but also factors affecting serotonin synthesis may be interesting and important points in acute pancreatitis.

High cellulose diet promotes intestinal motility through regulating intestinal immune homeostasis and serotonin biosynthesis

It is widely accepted dietary fiber intimately linked to inflammatory and nervous diseases, which often been described with altered gastrointestinal (GI) motility. However, how dose dietary fiber modulate inflammation and crosstalk influence GI function has not been explained in detail. We found fiber-free diet reduced intestinal motility, accompanied by upregulated proinflammatory immunocytes and inflammatory cytokines in colon of mice. We also discovered high-cellulose diet increased synthesis of serotonin and expression of neurotrophic factors, both of that have been reported involved in promoting intestinal motility. In addition, metabolomics analysis showed increased tryptophan metabolites in high-cellulose diet mice, which happened to be required for serotonin biosynthesis. Further analysis revealed high-cellulose diet changed the composition of gut microbiota, in particular by altering the ratio of Firmicutes to Bacteroidetes, consequently, concentration of short-chain fatty acids (SCFAs), especially acetate. Orally administration of acetate confirmed its modulating to serotonin synthesis, neurotrophic factors expression and immunocyte differentiation through regulating histone deacetylase (HDAC3) activity in colon. Together, our results demonstrated high-cellulose diet promote intestinal motility through regulating intestinal homeostasis and enteric nervous system by increasing acetate production and HDAC3 inhibition. Thus, rich cellulose diet or acetate supplement can be considered as dietary advice to improve clinically intestinal motility insufficiency.

Genetic Analysis of Tryptophan Metabolism Genes in Sporadic Amyotrophic Lateral Sclerosis

The essential amino acid tryptophan (TRP) is the initiating metabolite of the kynurenine pathway (KP), which can be upregulated by inflammatory conditions in cells. Neuroinflammation-triggered activation of the KP and excessive production of the KP metabolite quinolinic acid are common features of multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). In addition to its role in the KP, genes involved in TRP metabolism, including its incorporation into proteins, and synthesis of the neurotransmitter serotonin, have also been genetically and functionally linked to these diseases. ALS is a late onset neurodegenerative disease that is classified as familial or sporadic, depending on the presence or absence of a family history of the disease. Heritability estimates support a genetic basis for all ALS, including the sporadic form of the disease. However, the genetic basis of sporadic ALS (SALS) is complex, with the presence of multiple gene variants acting to increase disease susceptibility and is further complicated by interaction with potential environmental factors. We aimed to determine the genetic contribution of 18 genes involved in TRP metabolism, including protein synthesis, serotonin synthesis and the KP, by interrogating whole-genome sequencing data from 614 Australian sporadic ALS cases. Five genes in the KP (AFMID, CCBL1, GOT2, KYNU, HAAO) were found to have either novel protein-altering variants, and/or a burden of rare protein-altering variants in SALS cases compared to controls. Four genes involved in TRP metabolism for protein synthesis (WARS) and serotonin synthesis (TPH1, TPH2, MAOA) were also found to carry novel variants and/or gene burden. These variants may represent ALS risk factors that act to alter the KP and lead to neuroinflammation. These findings provide further evidence for the role of TRP metabolism, the KP and neuroinflammation in ALS disease pathobiology.

TPH1 Gene Polymorphism (rs211105) Influences Serotonin and Tryptophan Hydroxylase 1 Concentrations in Acute Pancreatitis Patients

Background: The role of serotonin and its metabolic pathway in the proper functioning of the pancreas has not been thoroughly investigated yet in the aspect of AP (acute pancreatitis). Tryptophan hydroxylase (TPH) as the rate-limiting enzyme of serotonin synthesis has been considered for possible associations in various diseases. Single-nucleotide polymorphisms (SNPs) in TPH genes have been already described in associations with psychiatric and digestive system disorders. Aim of this study was to explore association of rs211105 (T/G) polymorphism in TPH1 gene with tryptophan hydroxylase 1 concentrations in blood serum in population of acute pancreatitis patients, and to investigate this association with acute pancreatitis susceptibility. Results: To date, we have found an association between the presence of the T allele at the position rs211105 (OR = 2.47, 95% CI: 0.94-6.50, p = 0.06) under conditions of a decreased AP incidence. For TT and GT genotype in control group, the lowest concentration of TPH was associated with higher serotonin levels (TT: Rs=-0.415, p=0.0018; GT: Rs=-0,457, p=0.0066), while for AP group: the highest levels of TPH among TT genotype were associated with lower levels of serotonin (TT: Rs=-0.749, p=0.0000), and in GG genotype higher levels of TPH were associated with higher levels of serotonin (GG: Rs=-0.738, p=0.037).Conclusions: Here, the new insight of the potential role of selected genetic factor in pancreatitis development was brought. Not only the metabolic pathway of serotonin, but also factors affecting serotonin synthesis may be interesting and important point in acute pancreatitis.

Effects of oral administration of an aqueous ginger extract on anxiety behavior and tryptophan and serotonin metabolism in the rat

Background: Zingiber officinale (ginger) is used widely as a herb and medicine. It contains among its constituents 6-Gingerol (a phenol) and quercetin (a flavonoid) that possess anxiolytic and antidepressant properties, but the potential biochemical mechanism(s) of these effects has not been assessed, particularly in relation to serotonin synthesis and neurotransmission. Aims and Objectives: We investigated the anxiolytic-like activity of an aqueous ginger extract by evaluating its influence on behavior, and its effects on serotonin metabolism and on metabolism and disposition of the serotonin precursor tryptophan (Trp) in rats. Materials and Methods: An aqueous ginger extract was given orally in a single daily dose equivalent to 500 mg of ginger material per kg body weight for 3 weeks. The elevated plus maze test of anxiety and Trp metabolism and disposition and brain serotonin synthesis and turnover were assessed in Ginger-treated and control rats. Results: When compared with controls, ginger-treated rats showed a significant increase in the time spent in the open arm, indicative of decreased anxiety. However there was no effect on locomotor activity in open field test. The extract caused significant decreases in activities of liver Trp 2,3-dioxygenase and significant increases in concentrations of serum Trp and corticosterone and brain Trp, serotonin and the major serotonin metabolite 5-hydroxyindoleacetic acid. Conclusion: An aqueous ginger extract exerts an anxiolytic effect in a behavioral model of anxiety, which may be caused by increased serotonin synthesis, and influences tryptophan metabolism and disposition in a manner analogous to antidepressant drugs.