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Background: Disrupted circadian rhythms have been associated with the development of irritable bowel syndrome (IBS). In some IBS patients, the symptoms may present with circadian fluctuations. Enterochromaffin cells (EC cells) and tryptophan hydroxylase 1 (TPH1) - 5 - hydroxytryptamine (5 - HT) signaling pathway are currently recognized as the key pathophysiological mechanism of IBS. Aims: To explore whether Bmal1, the core circadian clock gene, is involved in the occurrence of IBS by regulating TPH1-5-HT signaling pathway in EC cells. Methods: Normal Sprague-Dawley (SD) rats and IBS-model SD rats, as well as wild type (WT) and intestine-specific Bmal1 knockout (Bmal1
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Objective@#To observe the pharmacodynamic effect of Xiaobanxia Decoction (XBXD) and categorized formula on cisplatin-induced delayed chemotherapeutic vomiting in rats, and to explore its prevention and treatment mechanism.@*Methods@#Sixty Wistar rats were randomly divided into blank group, model group, ondansetron group, XBXD group, Ginger Pinellia Decoction group and Pinellia and Dried Ginger Powder group, with 10 rats in each group. The ondansetron group was given 2.6 mg/(kg•d) ondansetron, the XBXD group was given XBXD 22 g/(kg•d), the Ginger Pinellia Decoction group was given 31.5 ml/(kg•d) Ginger Pinellia Decoction, and Pinellia and Dried Ginger Powder group was given 0.63 g/(kg•d) Dried Ginger Powder. The blank group and the model group were intragastrically administered with normal saline. All the treattmens were last for three days and twice per day. After the first administration, except the blank group, the rats in all groups were intraperitoneally injected with 6 mg/kg cisplatin to establish chemotherapy-induced vomiting model. The kaolin intake of the chemotherapical rats were weighed every 24 h, and the ileum and medulla 5-HT, 5-HIAA, TPH and MAOA levels were detected by ELISA.@*Results@#Compared with the model group, the kaolin intake of the chemotherapy rats in each treatment group significantly decreased (P<0.05). The levels of ileum 5-HT (308.04 ± 29.90 ng/L, 355.97 ± 19.16 ng/L, 389.97 ± 24.86 ng/L vs. 498.95 ± 13.92 ng/L) and medulla 5-HT (375.32 ± 19.33 ng/L, 395.18 ± 16.12 ng/L, 406.68 ± 12.09 ng/L vs. 478.52 ± 13.88 ng/L) in the XBXD group, Ginger Pinellia Decoction group and Pinellia and Dried Ginger Powder significantly decreased (P<0.05). The levels of ileum TPH (35.14 ± 2.68 ng/L vs. 47.31 ± 0.83 ng/L) in the XBXD group significantly decreased (P<0.05). The levels of medulla TPH (33.68 ± 2.79 ng/L, 38.19 ± 1.74 ng/L vs. 43.68 ± 1.53 ng/L) in the Ginger Pinellia Decoction group and Pinellia and Dried Ginger Powder significantly decreased (P<0.05). The levels of MAOA, 5-HIAA in the ileum and medulla of the XBXD group, Ginger Pinellia Decoction group and Pinellia and Dried Ginger Powder significantly decreased (P<0.05).@*Conclusions@#XBXD and categorized formula can effectively prevent and treat delayed chemotherapy-induced vomiting in rats, and its mechanism may be related to decrease the TPH level and inhibiting 5-HT synthesis.
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The biogenic monoamine 5-hydroxytryptamine (5-HT) is an ancient intracellular signaling molecule widely distributed in all animals with nervous systems, and has been implicated in principal behaviors. Tryptophan hydroxylase (TRH) induces a highly specific catalytic reaction that converts L-tryptophan (tryptophan) to 5-hydroxy-L-tryptophan (5-HTP) that is subsequently used as a substrate by aromatic L-amino acid decarboxylase (DDC) to form 5-HT. Five-HT is an ancient intracellular signaling molecule that is widely distributed in the animal kingdom and has been implicated in regulating the behaviors of animals with nervous systems. However, the role of TRH in Lepidoptera is not well understood. In this study, we cloned 1 667 bp cDNAs of Bombyx mori TRH (BmTRH), which contains a 1 632 bp open reading frame (ORF). Homology analysis revealed that BmTRH shared high amino acid identity with Homo sapiens TPH and Drosophila TRH (DmTRH). The high homology (70%) of BmTRH with DmTRH suggested that BmTRH could have a function similar to DmTRH. Gene expression analysis revealed that BmTRH was mainly expressed in head and central nervous (CNS). Moreover, immunohistochemistry and Western blotting analyses showed that BmTRH was detected only in larval nervous tissues. Taken together, our results indicate that BmTRH could likely function in the regulation of neural activities in B. mori. The transcripts of B. mori decarboxylase (BmDDC) and B. mori phenylalanine hydroxylase (BmPAH) whose proteins had TRH activity, were also expressed in the CNS tissues, indicating that unlike in Drosophila, two distinct mechanisms likely regulate 5-HT synthesis in silkworm.
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Animals , Amino Acid Sequence , Bombyx , Cloning, Molecular , DNA, Complementary , Insect Proteins , Phenylalanine Hydroxylase , Tryptophan HydroxylaseABSTRACT
Telotristat ethyl is a peripheral tryptophan hydroxylase (TPH) inhibitor for the treatment of carcinoid syndrome. Telotristat ethyl inhibits TPH,thereby reducing the production of serotoin(5-HT) and the daily bowel movement. Pharmacology, pharmacokinetics,clinical studies and safety of telotristat ethyl were reviewed in the paper. Telotristat ethyl has become a novel treatment option for carcinoid syndrome patients. Telotristat ethyl is well tolerated with low incidence of side effects.
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Objective To verify the interaction between single nucleotide polymorphism of trypto-phan hydroxylase 2 (TPH2) (rs4570625,rs11178997,rs120074175) and negative life events and the asso-ciation with major depressive disorder (MDD) in a Chinese population.Methods Totally 300 cases of pa-tients with major depressive disorder and 300 healthy controls in northern China were enrolled and the ge-nomic DNA were extracted. PCR was used to detect the polymorphisms of rs4570625, rs11178997, rs120074175.Questionnaire survey was conducted on the case group and the control group.Chi-square test was used to compare the differences in the frequency distribution of alleles and genotype between two groups. The generalized multifactor dimensionality reduction ( GMDR) method was used to analyze the interaction between gene and environment.Binary logistic regression was used to verify the optimal model.Results After adjusting the factors of sex and age,the GMDR analysis showed rs4570625,rs11178997,rs120074175 and negative life events were the optimal model.In this model, the testing balanced accuracy was 0.7838 and cross-validation consistency value was 10/10.There was statistically significant effect on the risk of major de-pressive disorder ( P ＝ 0.001 ). Binary logistic regression analysis showed that individuals, who had rs11178997 A+ genotype (AA,AT),rs120074175 A+genotype (AA,AG) and negative life events,had sig-nificant OR values of 24.307(95%CI＝13.007-45.427) and 38.2502(95%CI＝1.148-69.181),showing a higher risk of depression.Conclusion The interaction between TPH2 gene (rs11178997,rs120074175) and negative life events plays an important role in depression.
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Objective To explore the interaction between tryptophan hydroxylase 2(TPH2) gene polymorphisms (rs4570625,rs11178997) and serotonin 1A receptor (5-HT1A) gene polymorpbisms (rs878567,rs1364043,rs6265) and the association with major depressive disorder (MDD) in a Chinese Han population.Methods The DNA isolated from peripheral blood samples of 288 MDD patients 288 healthy subjects was detected by single base primer extension assay (Snapshot).The generalized multifactor dimensionality reduction (GMDR) method was used to analyze the gene-gene interaction.Results Significant differences were found in the genotype (patients (TT:27,TA:152,AA:109),controls (TT:82,TA:105,AA:101),P＜0.01) and allele(patients (T:206,A:370),controls (T:269,A:307),P＜0.01) frequencies of rs1 1178997 within TPH2 between MDD patients and controls.Statistically,a greater risk of developing MDD was found in individuals with an rs1 1178997 A-allele(OR=1.574,95％CI=1.243-1.993).The interaction between TPH2 (rs4570625,rs1 1178997) and 5-HT1A (rs878567,rs1364043,rs6265) was considered as the best multi-locus model,and this showed a testing accuracy of 57.67％ and a CV consistency of 10/10.And this interaction had a significant effect on the risk of MDD (P=0.0107).Conclusion There may be an association between the interaction of TPH2 and 5-HT1A polymorphisms and MDD.
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BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a multifaceted disorder that afflicts millions of individuals worldwide. IBS is currently diagnosed based on the presence/duration of symptoms and systematic exclusion of other conditions. A more direct manner to identify IBS is needed to reduce healthcare costs and the time required for accurate diagnosis. The overarching objective of this work is to identify gene expression-based biological signatures and biomarkers of IBS. METHODS: Gene transcripts from 24 tissue biopsy samples were hybridized to microarrays for gene expression profiling. A combination of multiple statistical analyses was utilized to narrow the raw microarray data to the top 200 differentially expressed genes between IBS versus control subjects. In addition, quantitative polymerase chain reaction was employed for validation of the DNA microarray data. Gene ontology/pathway enrichment analysis was performed to investigate gene expression patterns in biochemical pathways. Finally, since vitamin D has been shown to modulate serotonin production in some models, the relationship between serum vitamin D and IBS was investigated via 25-hydroxyvitamin D (25[OH]D) chemiluminescence immunoassay. RESULTS: A total of 858 genetic features were identified with differential expression levels between IBS and asymptomatic populations. Gene ontology enrichment analysis revealed the serotonergic pathway as most prevalent among the differentially expressed genes. Further analysis via real-time polymerase chain reaction suggested that IBS patient-derived RNA exhibited lower levels of tryptophan hydroxylase-1 expression, the enzyme that catalyzes the rate-limiting step in serotonin biosynthesis. Finally, mean values for 25(OH)D were lower in IBS patients relative to non-IBS controls. CONCLUSIONS: Values for serum 25(OH)D concentrations exhibited a trend towards lower vitamin D levels within the IBS cohort. In addition, the expression of select IBS genetic biomarkers, including tryptophan hydroxylase 1, was modulated by vitamin D. Strikingly, the direction of gene regulation elicited by vitamin D in colonic cells is “opposite” to the gene expression profile observed in IBS patients, suggesting that vitamin D may help “reverse” the pathological direction of biomarker gene expression in IBS. Thus, our results intimate that IBS pathogenesis and pathophysiology may involve dysregulated serotonin production and/or vitamin D insufficiency.
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Humans , Biomarkers , Biopsy , Cohort Studies , Colon , Diagnosis , Gene Expression Profiling , Gene Expression , Gene Ontology , Health Care Costs , Immunoassay , Irritable Bowel Syndrome , Luminescence , Oligonucleotide Array Sequence Analysis , Polymerase Chain Reaction , Real-Time Polymerase Chain Reaction , RNA , Serotonin , Transcriptome , Tryptophan , Tryptophan Hydroxylase , Vitamin D , VitaminsABSTRACT
ABSTRACT Objective: Identify whether rs11179000, rs136494 and rs4570625 polymorphisms of the tryptophan hydroxylase 2 gene, are associated with a major depressive disorder in a sample of the Colombian population. Methods: Case-control study was conducted in which a comparison was made between subjects diagnosed with major depressive disorder at some point in adulthood or active symptoms at the time of evaluation, and subjects with no psychiatric disease. Subjects were studied in the Department of Psychiatry, Faculty of Medicine and the Institute of Genetics at the National University of Colombia. Polymorphisms were genotyped using Taqman probes in real time PCR. As well as studying the association between major depressive disorder and these single nucleotide polymorphisms (SNPs), the association with other factors previously associated with depression were also analysed. Results: No statistically significant association between genotypic and allelic frequencies of each polymorphism and major depressive disorder was found. Association between sex and complication during pregnancy/childbirth and major depressive disorder was observed. Association between sex and complication during pregnancy/childbirth and major depres sive disorder was observed. Conclusions: There was no association between any polymorphism and major depressive disorder.
RESUMEN Objetivo: Identificar si los polimorfismos rs11179000, rs136494 y rs4570625 del gen de la triptófano hidroxilasa 2 están asociados a trastorno depresivo mayor en una muestra de población colombiana. Métodos: Estudio de casos y controles en el que se comparó a sujetos con trastorno depresivo mayor diagnosticado en algún momento de la vida adulta o con síntomas activos en el momento de la valoración y sujetos sin enfermedad psiquiátrica. Se estudió a los sujetos en el Departamento de Psiquiatría de la Facultad de Medicina y en el Instituto de Genética de la Universidad Nacional de Colombia. Se genotipificaron los polimorfismos usando reacción en cadena de la polimerasa en tiempo real y sondas Taqman. Además de buscar asociación entre trastorno depresivo mayor y estos polimorfismos de un solo nucleótido, se exploró asociación con otros factores relacionados previamente con depresión. Resultados: No se encontró asociación estadísticamente significativa entre las frecuencias genotípicas o alélicas de cada polimorfismo y el trastorno depresivo mayor. Se observó asociación entre sexo y complicaciones durante el embarazo/parto y trastorno depresivo mayor. Conclusiones: No se halló asociación entre polimorfismo alguno y el trastorno depresivo mayor.
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Humans , Male , Female , Adolescent , Adult , Case-Control Studies , Polymorphism, Single Nucleotide , Depressive Disorder, Major , Psychiatry , Tryptophan Hydroxylase , Polymerase Chain Reaction , Depression , Mental DisordersABSTRACT
OBJECTIVE:To provide basis and thinking for the development of medicines for treating depression. METHODS:Rats with adaptive feeding for 7 d were randomly divided into normal group,depression group and treatment group(citalopram hy-drobromide 1 mg/kg),8 in each group. Rats in depression group and treatment groups randomly received once low-density stimula-tion in a day [catching tail stimulation(1 min),frequent flashing stimulation(120 times/min,12 h),noise stimulation(4 h),ice water swimming stimulation(1 h),hot water stimulation(45 ℃,1 h),electric shocking foot(10 Hz,1 mA,each time interval of 100 ms,100 times),no food and no water(24 h)] for 21 d to reduce stress depression model. Body mass of rats in 0,7 d of adaptive feeding and 7,14,21 d of stress were respectively weighed,and horizontal activity and vertical activity frequencies in open field test were detected. After stress,rats were intragastrically administrated related medicines for 30 d,then 5-hydroxytrypta-mine (5-HT) and tryptophan hydroxylase (TPH) expressions in brain,liver,kidney tissues were determined. RESULTS:Com-pared with normal group,the increasing trend of body mass in depression group and treatment group slowed down from the 14 d of stress(P<0.05). The horizontal activity frequencies in depression group and treatment group in 14,21 d of stress slowed more ob-viously than the previous time point (P<0.05 or P<0.01);vertical activity frequencies in 21 d of stress slowed more obviously than the previous time point (P<0.05 or P<0.01). After 30 d of administration,horizontal activity and vertical activity frequen-cies in treatment group were increased more obviously than the previous time point (P<0.01). Compared with depression group,brain tissue of rats,indicating that TPH can be used as a target for depression treatment.
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Objective To evaluate the effect of ketamine on the expression of tryptophan hydroxylase 2 (TPH2) in the median raphe nuclei of mentally depressed mice.Methods Thirty-six healthy SPF male C57BL/6J mice,aged 8-12 weeks,weighing 20-26 g,were divided into 3 groups (n=12 each) using a random number table:control group (C group),depression group (D group) and depression plus ketamine group (D+K group).Mental depression was induced by forcing the animals to swim in a narrow cylinder from which they can not escape.Ketamine 15 mg/kg was intraperitoneally injected once a day for 7 consecutive days starting from 1 day after successful establishment of the model in group D+K.The equal volume of normal saline was given instead of ketamine in C and D groups_ Forced swimming test was performed again at 30 min after the last administration,and the immobility time was recorded.Open field test was also performed at 30 min after the last administration,and the total horizontal distance and the number of standing on the back legs were recorded.The mice were sacrificed after the end of the behavioral testing,and the hippocampi and median raphe nuclei were isolated.High-performance liquid chromatography-electrochemical detection assay was used to measure the content of 5-hydroxytryptamine (5-HT) in hippocampi.The expression of TPH2 protein and mRNA in the median raphe nuclei was detected using Western blot and real-time polymerase chain reaction,respectively.Results Compared with group C,the immobility time was significantly prolonged,the total horizontal distance was shortened,the number of standing on the back legs and content of 5-HT in hippocampi were deceased,and the expression of TPH2 protein and mRNA in the median raphe nuclei was down-regulated in group D,and the total horizontal distance was significantly shortened,the number of standing on the back legs was decreased (P＜0.05),and no significant change was found in the immobility time,content of 5-HT in hippocampi or expression of TPH2 protein and mRNA in the median raphe nuclei in group D +K (P＞0.05).Compared with group D,the immobility time was significantly shortened,the content of 5-HT in hippocampus was increased,the expression of TPH2 protein and mRNA in the median raphe nuclei was up-regulated (P＜0.05),and no significant change was found in the total horizontal distance or the number of standing on the back legs in group D+K (P＞0.05).Conclusion The mechanism by which ketamine produces anti-depressant effect may be related to up-regulation of TPH2 expression in the median raphe nuclei and increase in the synthesis of 5-HT in hippocampi of mice.
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The identity of higher-order neurons and circuits playing an associative role to control renal function is notwell understood.We identified specific neural populations of rostral elements of brain regions that project multisynaptically to the kidneys in 3~ days after injecting a retrograde tracer pseudorabies virus (PRV)-614 into kidney of 13 adult male C57BL/6J strain mice.PRV-614 infected neurons were detected in a number of mesencephalic (e.g.central amygdala nucleus),telencephalic regions and motor cortex.These divisions included the preoptic area (POA),dorsomedial hypothalamus (DMH),lateral hypothalamus,arcuate nucleus (Arc),suprachiasmatic nucleus (SCN),periventricular hypothalamus (PeH),and rostral and caudal subdivision of the paraventricular nucleus of the hypothalamus (PVN).PRV-614/Tyrosine hydroxylase (TH) double-labeled cells were found within DMH,Arc,SCN,PeH,PVN,the anterodorsal and medial POA.A subset of neurons in PVN that participated in regulating sympathetic outflow to kidney was catecholaminergic or serotonergic.PRV-614 infected neurons within the PVN also contained arginine vasopressin or oxytocin.These data demonstrate the rostral elements of brain innervate the kidney by the neuroanatomical circuitry.
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Tryptophan hydroxylase I (TPH1) catalases the 5-hydroxylation reaction of L-Trp, which is the rate-limiting step in the synthesis of serotonin. Serotonin, a major component of Bufonis venenum, is involved in numerous physiological functions as an important neurotransmitter. In this study, BbgTPH1 cDNA was cloned from the parotid gland of Bufo bufo gargarizans. Genetic engineering techniques were used to construct a recombinant prokaryotic fusion expression plasmid pMAL-BbgTPH1, and the induced conditions to express the recombinant BbgTPH1 in E. coli TB1 cells were optimized. The full length of BbgTPH1 is 1984 bp (GenBank accession No. JQ768313) with a 1443 bp open reading frame (ORF) encoding a 480 amino acid residues. The deduced protein molecular weight is 55.2 kDa and its theoretical isoelectric point is 5.58. The sequence includes conserved domain and special signal sequence of the aromatic amino acid hydroxylase (AAAH) superfamily. Homologous alignment showed that BbgTPH1 shared a high homology with other species. Phylogenetic tree showed the closest relative to BbgTPH1 was Xenopus tropical-TPH1. The best induction conditions of recombinant BbgTPH1 were 0.5 mmol·L-1 IPTG at 20℃ for 8 h. The function of BbgTPH1 was identified by in vitro enzymatic reaction and the recombinant BbgTPH1 was able to produce 5-hydroxytryptophan by catalyzing tryptophan. This study represents the first time of cloning and identification of the function of TPH1 in Bufo genus. The results of this study will be an important foundation for future studies of biosynthesis of bufotenines in the parotid gland of B. bufo gargarizans.
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Obiective To investigate the effects of antidepressant therapy on whole regulating function of serotonin and tryptophan hydroxylase 2 system in ovariectomized(OVX) rats with depressive disorder.Methods seventy-two female Sprague-Dawley rats were used as subjects.The rats were randomly divided in-to 8 groups as following:Sham operation group (Sn),depression group (Dn),the OVX group (On),OVX with depression group (ODn),OVX with depression + sertraline group (ODs),OVX with depression + citalopram group(ODx),OVX with depression+ venlafaxine group(ODw),OVX with depression+ reboxetine group(0Dr).Rats in group OVX and group OVX with depression were ovariectomized.Rats in group with depression were exposed to the chronic unpredictable mild stress (CUMS).Open-field test and sugar consumption experiment were tested on all rats before the experiment and the 28th day of experiment.The expression of TPH2 mRNA was measured with RT-PCR,and the expression of TPH2 protein was detected by Western blot.The concentration of 5-HT was detected by ELISA.Results (1) After exposure of CUMS,the scores of motion and percentage of sugar consumption experiment in Dn group were decreased contrast to the Sn group (P＜0.05),and the scores in ODn group were decreased compared with the on group(P＜0.05).(2)The protein and gene expression of THP2 in On and Dn group were decreased contrast to the Sn group (P＜0.05).The protein and gene expression of THP2 in ODn were decreased compared with the on group (P＜0.05).The protein and gene expression of THP2 in ODs (protein (0.68±0.07);gene (0.87±0.09)),ODx (protein (0.71 ±0.05);gene (0.84±0.17)),ODw(protein (0.69±0.04);gene (0.88±0.16)) and ODr(protein (0.53±0.07);gene (0.70±0.15)) were increased compared with the ODn(protein (0.31±0.09);gene (0.56±O.16)) group (P＜0.05).(3)The concentration of 5-HT of hippocampus and serum in Dn and On group were decreased contrast to the Sn group (P＜0.05).The concentration of 5-HT of hippocampus and serum in ODs,ODx,ODw and ODr group was increased compared with the ODn group (P＜0.05).Conclusion The antidepressants can up-regulate the expression of THP2 and the concentration of 5-HT in the OVX rats with depressive disorder.Sertralin is stronger however Reboxetine Mesylate is the poorest.
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Introduction: Suicide attempt (SA) is in the middle of continuum of complex suicidal behavior phenotype. Psychiatric disorders and acute stressful life events (SLEs) are triggers for suicidal behavior. Serotonin system genes are often implicated in suicidal behavior. Tryptophan hydroxylase 2 (TPH2), exclusively expressed in the brain, is the rate-limiting enzyme for serotonin biosynthesis. TPH2 may be enrolled in stress-response mechanisms via hypothalamic–pituitary–adrenal axis, while TPH2 variant rs7305115 has been reported to affect gene expression in postmortem human pons. To date, only poor examination of this variant in etiology of suicidal behavior has reported conflicting results. The aim of the present study was to assess rs7305115 main effect and its interaction with acute SLEs in SA pathology among Serbian psychiatric patients. Methods: 165 suicide attempters and 188 suicide non-attempters, suffering from major psychiatric disorders, participated in the study. Acute SLEs score was assessed using the List of Threatening Experiences Questionnaire. Variant rs7305115 was genotyped using TaqMan-based allelic discrimination assay. Statistical analyses were done in SNPstats by applying logistic regression adjusted by psychiatric diagnoses. Results: Variant rs7305115 was not associated with SA in Serbian psychiatric patients, neither alone, nor in combination with acute SLEs, for all five models of inheritance tested (P>0.05). Discussion: Our finding does not support the main and moderating implication of TPH2 variant rs7305115 in SA liability among Serbian psychiatric patients. Further examination in larger samples of this variant in SA patology is necessary due to its functional relevance.
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Objective To explore the effect of Chaihu Shugan Powder (CSP) on the content of 5-hydroxytryptamine (5-HT) in the hippocampus and the expression of tryptophan hydroxylase 2(TPH2) in median raphe nuclei in depression rats.Methods SD rats were randomly divided into normal group(n=12),model group (n=12),fluoxetine group (n=12),low-dose and high-dose CSP group (n =12,respectively).Depression model was made by reserpine intraperitoneal injection.During the experiment,the weight and the open-field scores were calculated;the content of 5-HT was detected by ELISA.The expression of TPH2 in median raphe nuclei was detected by Western blot.Results Compared with the weight ((225.02±5.23) g),the open-field scores ((12.6± 5.1)score) and content of 5-HT ((1.09±0.27) ng/ml) in the model group,high-dose CSP showed significantly improve the depressive rats in weight,open field score and content of 5-HT ((238.78±5.16) g,(15.6±7.8) score and (1.80±0.58) ng/ml,respectively;P＜0.05 or P＜0.01).The expression of TPH2 (0.66±0.21) in median raphe nuclei in the high-dose CSP group was apparently increased compared with that in the model group(0.16±0.04) (P ＜0.01).Conclusion CSP have the effects of anti-depression,which could be related with the increase of the 5-HT content in the hippocampus and the expression of TPH2 in median raphe nuclei.
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Objective To investigate the association of single nucleotide polymorphisms (SNPs) of loci rs4570625,rs11178997 at promoter region of tryptophan hydroxylase 2 (TPH2) genes with alcohol dependence and depressive symptom in the alcohol-dependent subjects in north Chinese Han people.Methods Genotype and allele frequencies of the TPH2 rs4570625 and rs1 1178997 polymorphisms were examined in 60 alcohol-dependent subjects (patient group) and 62 normal controls (control group) by Polymerase Chain Reaction (PCR) amplification and DNA sequencing techniques.The alcohol-dependent subjects were evaluated by 24 Hamilton Depression Scale (HAMD).Association analysis was carried out between the polymorphism and symptom of depression in the alcohol-dependent subjects.Results There were significantly statistical differences in the rs4570625 alleles (G and T) (x2 =5.280,P＜0.05),but no statistically significant differences in the genotypes (G/G,G/T,T/T) (x2 =5.078,P＞0.05) between patient group and control group.Significant statistically difference could be found in the rs4570625 alleles (G and T) between the alcohol-dependent subjects who had depressive symptoms and the subjects who did not have depressive symptoms (P＜0.05),but no significantly statistical differences could be found in the genotypes frequency (P＞0.05).No significant statistically differences in the genotype and allele frequencies of the rs 11178997 were observed between the alcohol-dependent subjects and normal controls and the alcohol-dependent subjects who had depressive symptoms and the subjects who did not have depressive symptoms (all P＞0.05).Conclusion The results suggest that the liability of alcohol dependence and depressive symptoms in alcohol-dependent subjects may be associated with the polymorphisms of TPH2 rs4570625 in north Chinese Han population,and the variant of the T allele may contribute to the morbidity.However,the polymorphisms of TPH2 rs1 1178997 may have no association with the susceptibility of alcohol dependence and the depressive symptoms accompanied with alcohol dependence.
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Aims: The existence of a dopamine (DA)-serotonin (5-HT) interaction in the brain has been validated by numerous studies. Nevertheless, interaction between DA- 5-HT synthesis in aging brain has not been highly considered. The central aim of this study was to investigate the interaction between DA and 5-HT synthesis in rat brain striatal synaptosomes. Methodology: Male Wistar rats (3 and 30 months old) were killed by decapitation and the brain sriatal synaptosomes were prepared by discontinuous Ficoll/sucrose gradient technique. DA or 5-HT synthesized during an appropriate incubation period was measured by the synaptosomes in the presence of added substrates (tyrosine or tryptophan) and a monoamine oxidase inhibitor (pargiline). Results: Dopamine synthesis in the synaptosomes prepared from young animals was markedly inhibited (about 30%) by the addition of 5 μM 5-HT and increasing 5-HT up to 50 μM caused only a relatively small additional inhibition. However, different concentrations of 5-HT (0-50μM) had little effect on dopamine synthesis of the synaptosomes preparations from old animals. In case of 5-HT synthesis, exogenously added 5 μM DA inhibited 5-HT synthesis in the synaptosomes of both ages by about 40%, whereas with higher concentration of DA (10-50 μM) the rate of inhibition was highly pronounced in the old rats as compared to that of young animals. Conclusion: It is concluded that DA- 5-HT cross reaction might be considered, where long-term treatment with L-DOPA of patients suffering from Parkinson's disease renders patients experience variations in response and even psychiatric problems.
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Objective To investigate the association of two functional polymorphisms of tryptophan hydroxylase 2(THP2) gene,rs4570625 and rs4565946,with poststroke anxiety disorders.Methods Totally 112 poststroke anxiety patients and 246 non-anxious stroke controls were included and completed Hamilton Anxiety Rating Scale.DNA was extracted from blood and genotyped for the two polymorphisms of THP2 gene by polymorphism chain reaction.Results The G allele of rs4570625 was associated with the increased risk of poststroke anxiety.Both the GG genotype and G allele were observed to be significantly higher in female case than in control.No significant difference in genotype and allele firequencies of the rs4565946 was found among the groups.Patients with the G-C haplotype had significantly increased the risk of poststroke anxiety compared to controls.Conclusions Our findings suggest that these ftmctional polymorphisms in TPH2 gene may be involved in development of poststroke anxiety.
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OBJECTIVES: Tardive dyskinesia (TD) is a serious and sometimes irreversible adverse effect that may develop during long-term antipsychotics treatment. Previous studies have suggested that brain serotonergic systems are related to TD vulnerability and tryptophan hydroxylase (TPH) is the rate limiting enzyme in the biosynthesis of serotonin. This study aimed to investigate the association between TPH2 gene -703G/T polymorphism (rs4570625) and antipsychotic-induced TD in the Korean schizophrenia patients. METHODS: We investigated whether TPH2 gene -703G/T polymorphism is associated with antipsychotic-induced TD in 280 Korean schizophrenia patients. The subjects with TD (n=105) and without TD (n=175) were matched for antipsychotic drug exposure and other relevant variables. RESULTS: There was no significant difference in the distribution of genotypic (chi2=3.00, p=0.223) and allelic (chi2=0.19, p=0.661) frequencies between patients group with TD and without TD. There was no significant difference in total Abnormal Involuntary Movement Scale score (F=1.95, p=0.362) among the genotype groups, either. CONCLUSIONS: The present study does not support that TPH2 gene -703G/T polymorphism is involved in TD of the Korean schizophrenia subjects.
Subject(s)
Humans , Antipsychotic Agents , Brain , Dyskinesias , Genotype , Movement Disorders , Schizophrenia , Serotonin , Tryptophan , Tryptophan HydroxylaseABSTRACT
OBJECTIVES: Tardive dyskinesia (TD) is a serious and sometimes irreversible adverse effect that may develop during long-term antipsychotics treatment. Previous studies have suggested that brain serotonergic systems are related to TD vulnerability and tryptophan hydroxylase (TPH) is the rate limiting enzyme in the biosynthesis of serotonin. This study aimed to investigate the association between TPH2 gene -703G/T polymorphism (rs4570625) and antipsychotic-induced TD in the Korean schizophrenia patients. METHODS: We investigated whether TPH2 gene -703G/T polymorphism is associated with antipsychotic-induced TD in 280 Korean schizophrenia patients. The subjects with TD (n=105) and without TD (n=175) were matched for antipsychotic drug exposure and other relevant variables. RESULTS: There was no significant difference in the distribution of genotypic (chi2=3.00, p=0.223) and allelic (chi2=0.19, p=0.661) frequencies between patients group with TD and without TD. There was no significant difference in total Abnormal Involuntary Movement Scale score (F=1.95, p=0.362) among the genotype groups, either. CONCLUSIONS: The present study does not support that TPH2 gene -703G/T polymorphism is involved in TD of the Korean schizophrenia subjects.