Effects of Tongxie-Yaofang on visceral sensitivity and expression of 5-HT and SERT in IBS-D model rats / 国际中医中药杂志

Objective:To explore the effect of Tongxie-Yaofang on visceral sensitivity in IBS-D and the possible mechanism. Methods:Divided 30 male SD rats (one-day old) into normal group (10 rats) and IBS-D model group (20 rats) randomly. IBS-D was induced by the method of neonatal maternal separation and restraint stress. After successful modeling, the IBS-D model group was randomly divided into model group and Tongxie-Yaofang group, with 10 rats in each group. Tongxie-Yaofang group was given Tongxie-Yaofang formula, 4.92 g/ml by gavage, while the normal and model groups were given the same amount of normal saline, rats were gavaged with 2 ml/100 g body weight once a day for 14 days. The electromyography of the exorectus muscle was used to meature colorectal distension and by using electronic constant pressure apparatus to evaluate visceral sensitivity. The morphology of colon by HE staining and Enzyme-linked immunosorbent assay (ELISA) were used to determine the level of colonic 5-hydroxytryptamine (5-HT), qPCR was used to detect the colonic mRNA expression of serotonin transporter (SERT) and Western blot was used to detect SERT expression in colon and hypothalamus. Results:Compared with the model group, at the expansion pressure of 60 mmHg and 80 mmHg, the electromyographic response [(179.51 ± 18.26)% vs. (226.42 ± 25.78)%; (242.13 ± 15.42)% vs. (306.02 ± 51.51)%] in Tongxie-Yaofang group was significantly decreased ( P<0.05 or P<0.01). The colonic content of 5-HT was significantly lower than that in the model group [(8.85 ± 0.53) ng/mg vs.(12.25 ± 1.95) ng/mg] ( P<0.01), the expression of SERT mRNA (0.85 ± 0.12 vs. 0.38 ± 0.02) and SERT protein (0.53 ± 0.11 vs. 0.36 ± 0.17) in the colon was significantly increased ( P<0.05 or P<0.01), the expression of SERT protein (0.88 ± 0.12 vs. 0.36 ± 0.13) in the hypothalamus was significantly increased ( P<0.05). Conclusion:Tongxie-Yaofang could relieve the visceral hypersensitivity, which may be achieved by regulating the 5-HT and SERT expression.

Effect of Tongxie Yaofang on Expressions of Colon SERT and Liver 5-HT2AR Proteins in Rats with Ulcerative Colitis Model of Liver Stagnation and Spleen Deficiency / 中国实验方剂学杂志

Objective:To observe the effect of Tongxie Yaofang on the expressions of colon serotonin transporter （SERT）， liver 5-hydroxytryptamine_2A receptor （5-HT_2AR） protein， serum 5-HT and inflammatory factors in ulcerative colitis （UC） model rats of liver stagnation and spleen deficiency， in order to explore the basis of syndrome of liver stagnation and spleen deficiency and the intervention mechanism of Tongxie Yaofang. Method:Fifty male SD rats were randomly divided into blank control group， model group， high， medium and low-dose Tongxie Yaofang group （10，5，2.5 g·kg^-1）， and salazosulacil group （0.3 g·kg^-1）. The ulcerative colitis model of liver depression and spleen deficiency was established by 2，4，6-trinitrobenzene sulfonic acid （TNBS）/ethanol solution enema + restraint stress + diet loss. After successful modeling， the samples were collected after 21 days of drug intervention. Htoxylin eosin （HE） staining and oil red staining were used to observe the pathological changes of colon and liver in each group. Serum interleukin-6 （IL-6）， IL-9， 5-HT and superoxide dismutase （SOD） were detected by enzyme linked immunosorbent assay （ELISA）. Protein expressions of SERT in the colons and 5-HT_2AR in liver of rats were detected by Western blot. Result:Compared with the normal group， obvious ulcers were formed in the colon and lipid droplets in the liver increased in the model group， serum levels of IL-6， IL-9 and 5-HT in the model group increased， while the level of SOD decreased （<italic>P</italic><0.05）. The protein expression of SERT in colon decreased， whereas the protein expression of 5-HT_2AR in liver increased （<italic>P</italic><0.05）. Compare with model group， the pathological damage of colon was improved， and the formation of lipid droplets in liver was reduced in high， medium-dose Tongxie Yaofang groups and sulfasalazine group. The serum levels of IL-6， IL-9 and 5-HT decreased， while the level of SOD increased in Tongxie Yaofang group and sulfasalazine group （<italic>P</italic><0.05）. The protein expression of SERT in colon increased in high，low-dose Tongxie Yaofang groups and sulfasalazine group， and the protein expression of 5-HT_2AR in liver decreased in medium， low dose Tongxie Yaofang groups and sulfasalazine group （<italic>P</italic><0.05）. Conclusion:Tongxie Yaofang may reduce the content of 5-HT， and regulate the intestinal motility and sensory system by up-regulating the expression of SERT in the colon， inhibit the expressions of IL-6，IL-9 and other inflammatory factors， and play an anti-inflammatory role， reduce the content of 5-HT and the expression of 5-HT_2AR in the liver， increase the level of SOD， regulate emotion and lipid metabolism in the liver， and then exert the intervention effect on ulcerative colitis with liver depression and spleen deficiency on the whole.

Effect of citalopram on miRNA-16/serotonin transporter pathway in peripheral blood of patients with depression / 上海交通大学学报（医学版）

Objective • To discuss the effects of citalopram on miRNA-16/serotonin transporter (SERT) pathway in peripheral blood of the patients with depression. Methods • Forty-five patients with depression without medication (untreated group), 32 patients with depression treated with medicine(drug treated group) and 32 healthy people (control group) were enrolled in the study. Hamilton Depression Scale-17 items were used to evaluate the depressive symptoms. The expression level of plasma miRNA-16 was detected by fluorescence quantitative PCR, and the level of SERT protein in platelets was detected by Western blotting. Fourteen of the baseline patients who were treated with citalopram were followed up for 2 months. After the follow-up, the evaluation of HAMD-17, the detection of miRNA-16 and SERT protein were conducted. Results • There was no significant difference in the expression level of plasma miRNA-16 among the three groups (F=0.421, P=0.657). There was no significant difference of SERT protein expression in the platelets among the three groups (F=0.112, P=0.894). The follow-up study showed that the HAMD-17 score decreased after 2 months (Z=.3.187, P=0.001), the average expression level of plasma miRNA-16 increased (t=2.455, P=0.032), and the expression of SERT protein in the platelets did not change (t=.0.750, P=0.470) in 14 patients who were treated with citalopram. Conclusion • Citalopram, a serotonin reuptake inhibitor, can down-regulate the expression of plasma miRNA-16 in patients with depression, and the decrease of the platelet serotonin is not caused by the decrease of SERT protein on platelet membrane, but may be related to the decrease of the SERT function.

Study the Association of Serotonin and Serotonin Transporter Concentration with Attention Deficit Hyperactivity Disorder in Sample of Iraqi Primary School Children

Objective: The current research focuses on neurotransmitter serotonin levels and the work was planned to study the comparison between children (female and male) as well as the special need children (with abnormal behaviors ADHD). Materials and methods: Total 86 children from certain primary school were selected, 56 of them were with ADHD (27 boys and 29 girls were present) and 30 healthy individuals (16 boy and 14 girls). ADHD was diagnosed by certain questionnaire form prepared for this study, blood samples were gathered, and were send for serotonin examination which was achieved with a certain enzyme linked immune sorbent assay (ELISA). Results were analyzed using special statistic program (SPSS version 18). Results: The collected data indicate that serotonin level was high (121.70 ± 4.05 ng/ml) in ADHD children compared with normal children (85.64 ± 2.43 ng/ml), and highly significant decrease in level of serotonin transporter in ADHD than in control samples (9.87 ± 0.29; 13.17 ± 0.50 ng/ml correspondingly). Conclusion: The increase and decrease in the level of serotonin serum and serotonin transporters could be related to the environmental issues that contribute to the disruption of behavior particularly rise in poor security and hot regions.

Association of the SLC6A4 gene 5HTTLPR polymorphism and ADHD with epilepsy, gestational diabetes, and parental substance abuse in Mexican mestizo children / Asociación del polimorfismo 5HTTLPR del gen SLC6A4 y TDAH con epilepsia, diabetes gestacional y adicción de los padres en niños mestizos mexicanos

Abstract Introduction Attention deficit hyperactivity disorder (ADHD) is one of the most common neuropsychiatric conditions in childhood and a multifactorial condition attributable to genetic and/or environmental influence. Allelic variants in the serotonin transporter gene (SLC6A4) have been associated to lower transcriptional efficiency, changes in serotonin concentration in several brain regions, and ADHD development. Objective To identify the association between the SLC6A4 alleles and ADHD diagnosis and risk factor phenotypes in children from a Mexican mestizo population. Method In this study, 134 unrelated children were included and evaluated for ADHD, genotypification for the 5HTTLPR polymorphism, and identification of multiple phenotypes from their clinical records and family background for association analysis. Results The following distribution of genotypes was observed: 23% SS, 49% SL, and 28% LL. From the phenotypes evaluated in the present study, gestational diabetes mellitus (p = .045), history of epilepsy (p = .047), and parental substance abuse (p = .033) showed an association with ADHD development in regression analysis along with the S variant. Discussion and conclusion Results suggest that interaction of the S allele and some of the phenotypes analyzed may play a relevant role in the development of ADHD in the studied population.

Resumen Introducción El trastorno por déficit de atención e hiperactividad (TDAH) es uno de los padecimientos neuropsiquiátricos más comunes en la infancia. Como su naturaleza es multifactorial, es atribuible a influencias genéticas y/o ambientales. Las variantes alélicas del gen transportador de serotonina (SLC6A4) se han asociado previamente con cambios en los niveles de serotonina en algunas regiones cerebrales, así como con el desarrollo de TDAH. Objetivo Identificar la posible asociación entre los alelos del gen SLC6A4 y el diagnóstico de TDAH, así como factores de riesgo en niños mestizos mexicanos. Método En el presente estudio se incluyeron 134 niños, los cuales fueron evaluados para TDAH, genotipificación del polimorfismo 5HTTLPR e identificación de múltiples fenotipos en su historia clínica y antecedentes familiares para su análisis de asociación estadística. Resultados Se mostró la siguiente distribución de genotipos: 23% SS, 49% SL y 28% LL. En un modelo de regresión, los fenotipos de diabetes mellitus gestacional (p = .045), historia de epilepsia (p = .047) y el abuso de sustancias de los padres (p = .033) mostraron asociación con la variante S y el desarrollo de TDAH. Discusión y conclusión El presente estudio sugiere que el alelo S en conjunto con algunos fenotipos puede cumplir un papel importante en el desarrollo de TDAH en nuestra población.

Effect of Stress and Serotonin-Transporter-Linked Polymorphic Region Variants on Internet Gaming Disorder in Korean Adults

OBJECTIVES: Internet gaming disorder (IGD) is known to be related to stress and the serotonin-transporter-linked polymorphic region (5-HTTLPR) that is known to be associated with stress and has been studied to affect various psychiatric illness outbreaks. We tried to examine the relationship between stress, 5-HTTLPR and IGD. METHODS: A total of 59 participants with IGD, diagnosed according to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria and 67 normal controls (NC) were enrolled. The IGD group and the NC were compared using chisquare test and independent sample t-test, and logistic regression analysis was used to examine the relationship between stress, the 5-HTTLPR, and IGD. RESULTS: The mean scores for anxiety, impulsivity and stress were significantly higher in the IGD group than in the NC. In addition, there was a significant association between stress and IGD [odds ratio (OR) = 1.172, 95% confidence interval (CI) = 1.008–1.362]. CONCLUSIONS: This study showed that stress would affect IGD. Therefore, the evaluation and management of stress should be included in the diagnosis and treatment of IGD.

Serotonin transporter promoter single nucleotide polymorphism susceptibility to chemotherapy-induced nausea and vomiting in colorectal cancer / 实用医学杂志

Objective To analyze the susceptibility of serotonin promoter single nucleotide polymorphism (SNP)rs956304 to chemotherapy-induced nausea and vomiting(CINV)in colorectal cancer.Methods Rs956304 genotypes and the clinical pathological data of 166 patients with colorectal cancer from September 2009 to April 2014 were retrospectively analyzed. Rs956304 genotype was analyzed by sequencing. The correlations between rs956304 genotype,factors of clinical pathology and CINV were analyzed by chi-square test. Unconditional logistic regression model was used to analyze the independent effect of rs956304 genotype on colorectal cancer CINV. Results Chi-square test showed that moderate to severe CINV was associated with rs956304 AG+GG genotype (P=0.011). Unconditional logistic regression model showed that the patients with AG+GG genotype had a signifi-cant higher risk of moderate to severe CINV than AA genotype(OR=3.215,95% CI:1.202 to 8.599,P=0.020). Conclusion Rs956304 AG+GG genotype is an independent risk factor for moderate to severe colorectal cancer CINV.

Polymorphism in the serotonin transporter protein gene in Maltese dogs with degenerative mitral valve disease

Degenerative mitral valve disease (DMVD) is the most commonly acquired cardiac disease in dogs. This study evaluated the relationship between genetic variations in the serotonin transporter (SERT) gene of Maltese dogs and DMVD. Genomic DNA was extracted from blood samples collected from 20 client-owned DMVD Maltese dogs and 10 healthy control dogs, and each exon of the SERT gene was amplified via polymerase chain reaction. The resulting genetic sequences were aligned and analyzed for variations by comparing with reference sequences; the predicted secondary structures of these variations were modeled and cross-verified by applying computational methods. Genetic variations, including five nonsynonymous genetic variations, were detected in five exons. Protein structure and function of the five nonsynonymous genetic variations were predicted. Three of the five polymorphisms were predicted to be probable causes of damage to protein function and confirmed by protein structure model verification. This study identified six polymorphisms of the SERT gene in Maltese dogs with DMVD, suggesting an association between the SERT gene and canine DMVD. This is the first study of SERT mutation in Maltese dogs with DMVD and is considered a pilot study into clinical genetic examination for early DMVD diagnosis.

Polimorfismos de número variable de repeticiones en tándem del intrón 2 de 5-htt y MUC 7 en pacientes venezolanos con asma o EPOC / 5-HTT intron 2 and MUC7 variable number of tandem repeats polymorphisms in a Venezuelan population with asthma or COPD

El asma y la enfermedad pulmonar obstructiva crónica (EPOC) son enfermedades inflamatorias crónicas. En ambas patologías existe broncoconstricción, producción de mediadores inflamatorios, hipersecreción de moco y migración de células inflamatorias. La serotonina tiene propiedades inmunomoduladoras que facilitan la broncoconstricción y su transportador (5-HTT) es el principal determinante de su concentración plasmática. Las mucinas (MUC) son glicoproteínas involucradas en la inmunidad innata local. El objetivo del presente trabajo fue estudiar la asociación entre polimorfismos de número variable de repeticiones en tándem (VNTR) del intrón 2 de 5-HTT (STin2) y MUC7 en pacientes venezolanos con asma o EPOC. El grupo de estudio consistió en 301 individuos (102 asmáticos, 99 EPOC, y 100 controles). No se observaron diferencias en las frecuencias de polimorfismos de MUC7 entre los grupos. Sin embargo, se encontró asociación entre alelos y genotipos de STin2 con presencia de asma o EPOC (p <0,001). El alelo STin2.9 tuvo un odds ratio (OR) de 0,15 (p=0,16) en los pacientes con asma, mientras que en los pacientes con EPOC los genotipos STin2.10/10 y 10/12 presentaron un OR de 0,33 (p=0,002) y 3,64 (p=0,002), respectivamente. Con relación a los haplotipos, el STin2/MUC7 10/10-6/6 se relacionó con riesgo en asma (OR=1,6, p=0,02) y protección en EPOC (OR=0,3, p=0,006) y el 10/12-6/6 (OR=3,7, p=0,002) fue un factor de riesgo para EPOC. En conclusión, en la población venezolana los polimorfismos de STin2 son importantes para definir factor de riesgo de enfermedad y, en consecuencia, el transportador de serotonina es relevante en ambas patologías.

Asthma and Chronic Obstructive Pulmonary Disease (COPD) are chronic inflammatory diseases. Both entities are characterized by bronchoconstriction, production of inflammatory mediators, mucus hypersecretion and inflammatory cell migration. Serotonin has immunomodulatory properties facilitating bronchoconstriction and its plasma concentration is transporter dependent (5-HTT). Mucins are glycoproteins involved in local innate immunity. The aim of this study was to assess the association between the variable number of tandem repeat polymorphisms (VNTR) of intron 2 of the serotonin ransporter (5-HTT) (STin2) and MUC7 in Venezuelan asthmatic or COPD patients. The group consisted of 301 individuals (102 asthmatics, 99 with COPD and 100 controls). There were no differences in the frequencies of MUC7 polymorphisms among the groups. However, there is a significant association between some alleles and genotypes with the presence of asthma or COPD (p <0.001). The STin2.9 allele had an odds ratio (OR) of 0.15 (p=0.16) in patients with asthma, while in patients with COPD, the STin2.10/10 and 10/12 genotypes had 0.33 (p=0,002) and 3.64 (p=0,002) OR, respectively. Regarding haplotypes, the STin2/ MUC7 10/10-6/6 is related to asthma risk (OR = 1.6, p=0.02) and COPD protection (OR=0.3, p=0.006) and 10/12-6/6 (OR=3.7, p=0.002), is a risk factor for COPD. In conclusion, in the Venezuelan population STin2 polymorphisms are important to define disease risk factor and consequently, the serotonin transporter is relevant to both pathologies.

Abuse-related effects of synthetic cathinones:importance of DAT/SERT relationships / 中国药理学与毒理学杂志

OBJECTIVE Wide spread abuse of synthetic cathinones found in bath salts preparations has resulted in regulation of some cathinones internationally. Chemists skirt these laws by altering the chemical structures of first-generation cathinones (ie, MDPV, methylone, and mephedrone), resulting in second-generation cathinones (eg, α-PVP, α-PPP, MDPPP, and MDPBP). Although MDPV is a more effective reinforcer than cocaine, little is known about the reinforcing effectiveness of second-generation cathinones. To test the hypothesis that synthetic cathinones with higher selectivity for DAT relative to SERT are more effective reinforcers. METHODS Monoamine transporter inhibition was determined using synaptosomes prepared from rat brains. The relative reinforcing effectiveness of intravenously self-administered MDPV, MDPBP, MDPPP, α-PVP, α-PPP, and cocaine were directly compared through evaluations of ① dose- response curves under a progressive ratio (PR) schedule of reinforcement and ② demand curves obtained for each drug in male Sprague-Dawley rats. RESULTS Rank order selectivity for DAT/SERT was α-PVP>MDPV>α-PPP≈MDPBP>MDPPP>cocaine. Comparisons of the maximum number of infusions obtained under a PR schedule of reinforcement (α-PVP>MDPV>α-PPP>MDPBP≈MDPPP>cocaine) and the essential value obtained for each drug in demand analyses (α-PVP>MDPV>α-PPP≈MDPBP≈MDPPP>cocaine) suggest relative reinforcing effectiveness is related to DAT/SERT selectivity. CONCLUSION These data provide evidence that DAT/SERT selectivity accounts for select synthetic cathinones functioning as more effective reinforcers than cocaine and may predict the abuse-related effects of novel synthetic cathinones in humans.

The association of the polymorphism of the 5-HTT gene with alcohol use disorders / 中华行为医学与脑科学杂志

Objective To investigate the possible associations of two polymorphisms (5-HTTLPR and STin2VNTR)of the serotonin transporter gene with alcohol use disorders (AUD).Methods 281 AUD cases (AUDIT score≥ 10) and 277 healthy controls (AUDIT score ≤5) were recruited in this study.All participants were genotyped using the PCR technique.Results The frequency of the L-allele of the 5-HTTLPR was 39.01％,and the 10-allele of STin2VNTR was 8.42％ in this population,the allele frequencies of both polymorphisms were consistent with Asian normal populations.No significant association was observed between 5-HTTLPR and AUD,but the genotypic and allele frequencies of the STin2VNTR were significant different between two groups even after Bonferroni adjustment,the 12 repeat allele of the STin2VNTR was significantly associated with the risk effect for AUD.Haplotype analysis for those two polymorphisms revealed no association between 4 haplotype combinations and AUD.Conclusion There is no relationship between 5-HTTLPR and AUD.The STin2VNTR polymorphism of 5-HTT may play a role in the pathogenesis of AUD.

Effects of intestinal microbiota of patients with chronic constipation on the expression of serotonin transporter and the bowel movement in mice / 中华消化杂志

Objective To investigate the effects of intestinal microbiota of patients with chronic constipation on the expression of serotonin transporter (SERT) and the bowel movement in mice.Methods Fecal samples of patients with slow transit constipation met Rome Ⅲ criteria and healthy normal controls were collected and made into fecal microbiota solution.Twenty specfic pathogen free (SPF) mice were divided into experiment group and control group.The mice of two groups were both pre-treated with streptomycin to establish the germ-free mice model.The mice of control group were gavaged with mixed fecal microbiota solution of healthy normal controls and the mice of experiment group were gavaged with mixed fecal microbiota solution of patients with chronic constipation.Mice were sacrificed after fed for 15 days.Defecation parameters and ink discharge time of mice were detected.The expressions of SERT mRNA and SERT protein in mice intestinal tissues were detected with real time-polymerase chain reaction and Western blotting.The 5-hydroxytryptamine (5-HT) levels of mice intestinal tissues were evaluated by enzyme-linked immunosorbent assay (ELISA) and double immunofluorescent staining.The methods of t test and Chi-square test were performed for statistical analysis.Results On the 15th day,the total number of the feces within 2 h of the experiment group and control group was 8.55±1.83 and 12.14±2.90,respectively,and the difference was statistically significant (t=3.33,P＜0.05).The weight of feces were (151.90 ± 32.42) mg and (246.72 ± 64.01) mg,respectively,and the difference was statistically significant (t=4.18,P＜0.01).The dry weight of feces were (65.52±11.76) mg and (92.93±23.07) mg,respectively,and the difference was statistically significant (t=3.37,P＜0.05).The water content of feces were (56.63 ± 3.01) ％ and (61.95 ± 3.70) ％,respectively,and the difference was statistically significant (t=3.57,P＜0.05).The defecating time of first black feces of the experiment group and control group were (83.24±11.31) min and (69.06±2.72) min,respectively,and the difference was statistically significant (t=-2.74,P＜0.05).The expressions of SERT mRNA and SERT protein levels in mice intestine tissues of the experiment group were significantly higher than those of the control group (t =2.61,-6.89;both P＜0.05).5-HT level of mice intestinal tissues of the experimental group and control group were (151.69± 10.18) ng/mL and (198.77 ± 25.99) ng/mL,respectively,and the difference was statistically significant (t=-4.13,P＜0.01).Conclusion Intestinal microbiota of patients with chronic constipation may influence the expression of SERT in the mice intestinal tissues,and then decrease the level of 5-HT,slowing the bowel movement in mice.

Effect of acupuncture treatment on gene expression of neurotransmitters of brain tissue in rats with post-stroke depression / 中国针灸

<p><b>OBJECTIVE</b>To observe the effects of acupuncture on mRNA of the neurotransmitter serotonin transporter (5-HTT), 5-HTreceptor (5-HTR), norepinephrineα2 receptor (NEαR) in brain tissue in rats with post-stroke depression.</p><p><b>METHODS</b>Forty male SD rats were randomly divided into a normal group, a model group, a medication group and an acupuncture group, 10 rats in each one. The model of post-stroke depression was established by occlusion of middle cerebral artery and chronic unpredictable mild stress method. After model was successfully established, the rats in the normal group and model group received no treatment; the rats in medication group were treated with intragastric administration of fluoxetine (2 mg/kg); the rats in acupuncture group were treated with acupuncture at "Baihui" (GV 20), "Fengfu" (GV 16), "Shenmen" (HT 7) and "Taichong" (LR 3) for 20 min, during which manual stimulation was given once, once a day, 7 days as one course, and totally 3 courses were given with an interval of one day between courses. The changes of rat behavior and 5-HT, NE were observed after intervention; the RT-PCR method was applied to observe the mRNA of 5-HTT, 5-HTR, NEαR in hippocampus, raphe nucleus and locus coeruleus.</p><p><b>RESULTS</b>After treatment, compared with the normal group, the Zea Longa score in the model group was increased, while sugar water consumption, the number of horizontal and vertical movement of open-field test was reduced (all<0.01); compared with the model group, the Zea Longa score in the medication group and acupuncture group was reduced, while sugar water consumption, the number of horizontal and vertical movement of open-field test were increased (<0.01,<0.05); compared between the medication group and acupuncture group, the behavior changes were not significantly different (all>0.05). After treatment, compared with the normal group, the content of 5-HT and NE in brain tissue and mRNA expression of 5-HTT, 5-HTR in hippocampus, raphe nucleus and locus coeruleus in the model group were reduced (all<0.01), but the mRNA expression of NEαR was increased (<0.01);compared with the model group, the content of 5-HT and NE in brain tissue and mRNA expression of 5-HTT, 5-HTR in hippocampus, raphe nucleus and locus coeruleus in the medication group and acupuncture group were increased (<0.01,<0.05), while the mRNA expression of NEαR was reduced (all<0.01). The differences between medication group and acupuncture group were not significantly different (all>0.05).</p><p><b>CONCLUSIONS</b>Acupuncture could significantly improve behavioral change in rats with post-stroke depression, which may be related to the regulation of 5-HT, NE in cerebral cortex as well as mRNA expressions of 5-HTT, 5-HTR, NEαR in hippocampus, raphe nucleus and locus coeruleus.</p>

Improvement of NET and 5-HTT expression involved in the anti-depressive effect of valproate / 中国药科大学学报

@#This study aimed at investigating the correlations between antidepressive effect of valproate and improvements of NET and 5-HTT expression in depressive rats leaded by chronic mild unpredicted stress(CUMS)with solitary condition. Sixty male SD rats were divided into normal group(NG), model group(MG), valproate treated-normal group(VNG), and valproate treated-model group(VMG), randomly. The changes of depressive behaviors were evaluated by the open-field test and force swimming test. The contents of MDA, activities of SOD and CAT in serum, the mRNA and protein expression of NET, 5-HTT in hippocampus were determined by biochemical methods, Real-time PCR and Western Blot, respectively. Results showed that CUMS can significantly decrease the activities in open-field test, SOD and CAT activities in serum, expression of 5-HTT in hippocampus, and obviously increase the immobility time in force swimming test, the level of MDA and expression of NET. The treatment of valproate obviously improved the changes induced by CUMS. However, the treatment of valproate had no significant influences on behaviors of NG rats. So, it revealed that improvements of the mRNA and protein expression of NET, 5-HTT may be involved in the antidepressive effect of valproate.

The correlation between 5-serotonin transporter gene polymorphism and the first episode major de-pressive disorder and cognitive function in adolescents / 中华行为医学与脑科学杂志

Objective To study the correlation between 5-serotonin transporter ( 5-HTT) gene pol-ymorphism and the first episode major depressive disorder ( MDD ) and cognitive function in adolescent. Methods 5-HTT genotype and allele were detected by polymerase chain reaction ( PCR) amplification of 76 patients with first episode of MDD and 73 normal controls. Case control method was used to analyze the correlation between different genotypes and the onset, the clinical features, and cognitive function. Result-s There was no significant difference between 5-HTTLPR genotype frequencies for the 41 cases of type S/S (53.9%),27 cases of type L/S(35.5%),8 cases of type L/L(10.5%)of case group and 5-HTTLPR geno-type frequencies for the 38 cases of type S/S(52.1%),18 cases of type L/S(24.7%),17 cases of type L/L (23.3%) of control group(P>0.05).Patients with S/S type,L/S type had significantly higher sleep scores than those of patients with type L/L(P=0.005,P=0.001). Agitation score in patients with S/S type group was significantly higher than that in patients with S/L,L/L(P=0.000,P=0.001);patients with S/S inferior-ity scores were significantly lower than those of patients with S/L,L/L(P=0.002,P=0.006). There was no significant difference in cognitive function among three groups. Conclusions In Chinese Han population, there may be no direct association between 5-HTTLPR gene polymorphism and susceptibility to MDD and its cognitive function in adolescents. S/S and L/S patients may be prone to sleep problems,type S/S patients may be prone to irritability and type L/L patients may be prone to inferiority.

Effect of ginsenoside Rb1 on proliferation and serotonin transporter and 5-HT1 B R expression in hypoxia-induced rat pulmonary artery smooth muscle cells via Rho/Rho-kinase pathway / 中国病理生理杂志

[ ABSTRACT] AIM:To observe the effect of ginsenoside Rb 1 on the proliferation and the expression of serotonin transporter (SERT), 5-hydroxytryptamine 1B receptor (5-HT1BR) in rat pulmonary artery smooth muscle cells (PASMCs) under hypoxia condition and the relationship with Rho /Rho-kinase signal pathway .METHODS: PASMCs were isolated from the adult male SD rats and primarily cultured .The subcultured cells from the 4th generation to the 6th generation were harvested and divided into normal group , and hypoxia group , different concentrations of Rb 1 incubation groups treated with 50, 100 and 200 mg/L ginsenoside Rb1 under hypoxia (HR50, HR100 and HR200 groups, respectively).The viability of the PASMCs was measured by CCK-8 assay.BrdU positive cells were determined using flow cytometry .The expression of serotonin transporter and 5-HT1BR at mRNA and protein levels was detected by RT-PCR and Western blot, respectively. The PASMCs were randomly divided into normal group , hypoxia group , HR200 group and hypoxia +Y-27632 incubation group ( HY group ) .The mRNA expression of Rho-kinase and phosphorylated myosin phosphatase target subunit 1 ( p-MYPT1) protein level were investigated by RT-PCR and Western blot, respectively.RESULTS: Compared with normal group, the proliferation of PASMCs in hypoxia group was significantly increased (P<0.01).The cell viability and the ex-pression of SERT and 5-HT1B R at mRNA and protein levels in all different concentrations of Rb 1 groups were obviously de-creased compared with hypoxia group ( P<0.05 ) .The mRNA expression of Rho-kinase and protein level of p-MYPT1 were markedly decreased in HR200 group, and no significant difference compared with HY group was observed ( P <0.01).CONCLUSION: Treatment with ginsenoside Rb1 might prevent hypoxia-induced proliferation of PASMCs and over-expression of SERT and 5-HT1B R through inhibiting the Rho/Rho-kinase pathway .

Associations between Serotonergic Genes and Escitalopram Treatment Responses in Patients with Depressive Disorder and Acute Coronary Syndrome: The EsDEPACS Study

Genes related to serotonin are associated with responses to treatment for depression. We examined associations between the serotonin transporter (5-HTT) and serotonin 2a receptor (5-HTR2a) genes and responses to treatment for depressive disorders in acute coronary syndrome (ACS). A total of 255 patients who met the DSM-IV major or minor depressive disorder and recently developed ACS were randomly assigned to the escitalopram (n=127) or placebo (n=128) group in this 24-week double-blind trial (ClinicalTrial.gov identifier: NCT00419471). Remission was defined as a Hamilton Rating Scale for Depression (HAMD) score < or =7. Assays were performed for the 5-HTTLPR, STin2 VNTR, 5-HTR2a 102T/C, and 5-HTR2a 1438A/G genotypes. Escitalopram was superior to placebo for treating depressive disorder with ACS but there were no significant associations between serotonergic genes and treatment responses even when considering ACS severity. The effect of escitalopram was independent of 5-HTT and 5-HTR2a polymorphisms.

Association of serotonin transporter (SLC6A4) & receptor (5HTR1A, 5HTR2A) polymorphisms with response to treatment with escitalopram in patients with major depressive disorder : A preliminary study.

Background & objectives: Genetic factors have potential of predicting response to antidepressants in patients with major depressive disorder (MDD). In this study, an attempt was made to find an association between response to escitalopram in patients with MDD, and serotonin transporter (SLC6A4) and receptor (5HTR1A, 5HTR2A) polymorphisms. Methods: Fifty five patients diagnosed as suffering from MDD, were selected for the study. The patients were treated with escitalopram over a period of 6-8 wk. Severity of depression, response to treatment and side effects were assessed using standardised instruments. Genetic variations from HTR1A (rs6295), HTR2A (rs6311 and rs6313) and SLC6A4 (44 base-pair insertion/deletion at 5-HTTLPR) were genotyped. The genetic data of the responders and non-responders were compared to assess the role of genetic variants in therapeutic outcome. Results: Thirty six (65.5%) patients responded to treatment, and 19 (34.5%) had complete remission. No association was observed for genotype and allelic frequencies of single nucleotide polymorphisms (SNPs) among remitter/non-remitter and responder/non-responder groups, and six most common side-effects, except memory loss which was significantly associated with rs6311 (p=0.03). Interpretation & conclusions: No significant association was found between the SNPs analysed and response to escitalopram in patients with MDD though a significant association was seen between the side effect of memory loss and rs6311. Studies with larger sample are required to find out genetic basis of antidepressant response in Indian patients.

Possible Association between Serotonin Transporter Gene Polymorphism and Suicide Behavior in Major Depressive Disorder

OBJECTIVE: The serotonin transporter (5-HTT) genes are major candidate genes for modulating the suicidal behavior. We investigated the association between serotonin transporter polymorphisms and suicidal behavior in patients with major depressive disorder (MDD). METHODS: Serotonin transporter intron 2 VNTR polymorphism (5-HTTVNTR) and serotonin transporter linked polymorphic region polymorphism (5-HTTLPR) were analyzed in 132 depressed patients with suicidal attempt as well as in 122 normal controls. Hamilton's 17-item Depression Rating Scale (HDRS), the Risk-Rescue rating system (RRR) and the Lethality Suicide Attempt Rating Scale updated (LSARS-II) were assessed for the depressed patients. RESULTS: Although not statistically significant, a trend was found such that the 10/10 and 10/12 alleles of 5-HTTVNTR were more common in suicidal subjects than in control subjects. Comparing allele frequency, those with a 10 allele or 10 allele carriers were higher in suicidal subjects than in control subjects. No difference was noted in 5-HTTLPR genotypes and haplotype distribution between the suicidal subjects and control subjects. The RRR scores in subjects with the 10/10 5-HTTVNTR genotype or 10 5-HTTVNTR allele were significantly lower than those in subjects with other genotypes. CONCLUSION: These results show the possibility that 10 allele of 5-HTTVNTR is related to suicidal behavior in the suicidal subjects with MDD and suggest that 12 allele of 5-HTTVNTR might be related to more lethality in the suicidal subjects with MDD.

Lack of association between the 5-HTTLPR and positive screening for mental disorders among children exposed to urban violence and maltreatment

Objective: To ascertain whether genetic variations in the serotonin transporter gene (5-HTTLPR 44-bp insertion/deletion polymorphism) influence an increase in depressive and anxiety symptoms in children and adolescents exposed to high levels of violence. Methods: Saliva samples were collected from a group of children who were working on the streets and from their siblings who did not work on the streets. DNA was extracted from the saliva samples and analyzed for 5-HTTLPR polymorphism genotypes. Results: One hundred and seventy-seven children between the ages of 7 and 14 years were analyzed (114 child workers and 63 siblings). Data on socioeconomic conditions, mental symptoms, and presence and severity of maltreatment and urban violence were collected using a sociodemographic inventory and clinical instruments. There was no positive correlation between the 5-HTTLPR polymorphism and presence of mental symptoms in our sample, although the children were exposed to high levels of abuse, neglect, and urban violence. Conclusions: Despite previous studies that associated adult psychiatric disorders with the 5-HTTLPR polymorphism and a history of childhood maltreatment, no such association was found in this sample of children at risk. .