Association study of interaction of tryptophan hydroxylase 2 with serotonin 1A receptor gene polymorphism on major depressive disorder / 中华行为医学与脑科学杂志

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.

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>

Genetic Polymorphism of 1019C/G (rs6295) Promoter of Serotonin 1A Receptor and Catechol-O-Methyltransferase in Panic Disorder

OBJECTIVE: Family and twin studies have suggested genetic liability for panic disorder (PD) and therefore we sought to determine the role of noradrenergic and serotonergic candidate genes for susceptibility for PD in a Japanese population. METHODS: In this age- and gender-matched case-control study involving 119 PD patients and 119 healthy controls, we examined the genotype distributions and allele frequencies of the serotonin transporter gene linked polymorphic region (5-HTTLPR), −1019C/G (rs6295) promoter polymorphism of the serotonin receptor 1A (5-HT1A), and catechol-O-methyltransferase (COMT) gene polymorphism (rs4680) and their association with PD. RESULTS: No significant differences were evident in the allele frequencies or genotype distributions of the COMT (rs4680), 5-HTTLPR polymorphisms or the −1019C/G (rs6295) promoter polymorphism of 5-HT1A between PD patients and controls. Although there were no significant associations of these polymorphisms with in subgroups of PD patients differentiated by gender or in subgroup comorbid with agoraphobia (AP), significant difference was observed in genotype distributions of the −1019C/G (rs6295) promoter polymorphism of 5-HT1A between PD patients without AP and controls (p=0.047). CONCLUSION: In this association study, the 1019C/G (rs6295) promoter polymorphism of the 5-HT1A receptor G/G genotype was associated with PD without AP in a Japanese population.

Association of Serotonin 1A Receptor Polymorphism with Variation in Health-Related Quality of Life in Korean Hemodialysis Patients

OBJECTIVE: Hemodialysis patients may have psychological distress and reduced quality of life (QoL) related to chronic physical health problems. Genetic polymorphisms associated with reduced QoL in hemodialysis patients. The aim of this study was to investigate the relationship between genetic polymorphisms and variation in health-related QoL in Korean hemodialysis patients. METHODS: The 36-item Short-Form Health Survey and the Korean Hospital Anxiety and Depression Scale were used to assess health-related QoL and psychological distress, respectively. Twenty hundred and five clinically stable patients from 6 hemodialysis centers have participated with informed consents. Sociodemographic factors, clinical factors, and genotypes of serotonin 1A receptor, brain-derived neurotrophic factors, and glucocorticoid receptor were assessed. Independent t-tests, correlation analyses, multiple regression analyses were performed for statistical analyses. RESULTS: The serotonin 1A receptor CC genotype group showed significantly higher physical and mental QoL levels than those with the GG/GC genotypes. In the final linear regression analysis, serotonin 1A receptor CC genotype was significantly associated with positive physical and mental QoL levels. CONCLUSION: ConclusionaaSerotonin 1A receptor polymorphism, as well as age and depression, were significantly associated with mental and physical QoL in hemodialysis patients. Functional activity in the serotonin receptor system may have a modulating effect on health-related QoL in hemodialysis patients.

Mechanisms of serotonin transporter and serotonin 1A receptor in the different susceptibility of chronic unpredictable stress / 中华行为医学与脑科学杂志

Objective To investigate the expression of serotonin transporter (5-HTT) and serotonin 1A treceptor (5-HT1 A R) located in the chronic unpredictable stress (CUS)-relative brain areas (mPFC,VTA,NAc) in high and low CUS susceptibility rats,thus to unveil the possible mechanism lead to the different CUS susceptibility.Methods One hundred and fifty male Sprague-Dawley rats were randomly assigned into experiment group (n =120) and control group (n =30).Rats in experiment group were trained according to established CUS procedure.OFT and FST were used to assess the different susceptibility to CUS:high susceptibility group (H group)and low susceptibility group (L group).After the model was established,rats were scarified and cardio-perfused,and the brains were removed and sliced up coronarily.The sections including ventral tegmental area (VTA),nucleus accumben (NAc),medial prefrontal cortex (mPFC) were selected.The mRNA levels of 5-HTT and 5-HT1AR in the regions were estimated with in situ hybridization.Results The expression of 5-HTT in H group were significantly lower than that of in the control and L group in all regions (mPFC:169.20 ± 8.23 vs 143.53 ±5.31 ; Nac:177.41 ± 5.68 vs 158.65 ± 5.24 ; VTA:174.16 ± 5.61 vs 158.65 ± 4.85),and the difference between the H and L group was significant(P＜0.01) ;however,the expression of 5-HT1AR in H group were significantly higher than that of in the control and L group in all regions (mPFC:113.98 ± 7.46 vs 125.90 ± 3.30 ; Nac:112.11± 5.50 vs 125.06 ± 3.97 ;VTA:103.11 ± 6.05 vs 115.57 ± 3.19),and the difference between the H and L group was significant (P＜ 0.01).Conclusion The overexpression of 5-HT1AR and down regulation of 5-HTT in the circuit of VTA-NAc-mPFC may be the basis of the high susceptibility to CUS.

Visualization of serotonin 1A receptor trafficking in neuron-like PC12 cells / 基础医学与临床

Objective To explore the mechanisms of trafficking and signaling of serotonin 1A receptor(5-HT_(1A))and its spatiotemporal distribution in living cells.Methods The mouse 5-HT_(1A) gene amplified by RT-PCR was recombined into pEGFP-N1 vector and the EGFP coding sequence was located in-frame at the C-terminal end of the 5-HT_(1A) receptor.The 5-HT_(1A)-EGFP was transfected into neuron-like PC12 cells as well as HEK293.The transfected cells were visualized using confocal microscopy,the mobility of 5-HT_(1A)-EGFP was monitored by live measurements and fluorescence recovery after photobleaching.Results The 5-HT_(1A) gene was identitical with the published gene sequence NM_008308.4 and a 5-HT_(1A)-EGFP fusion construct was created.After stable transfection of the plasimd into a PC12 cell line and analysis with a confocal laser scanning microscopy,the EGFP-tagged 5-HT_(1A) was predominantly associated with the plasma membrane,but some intracellular vesicles in the perinuclear region also contained the fusion protein.The predominant localization of 5-HT_(1A)-EGFP at the plasma membrane was confirmed in transiently transfected HEK293 cells.Bleached fluorescence was partialy recovered in 100 seconds,indicating that the 5-HT_(1A)-EGFP was mobiled on the membrane.Conclusion Spatiotemporal distribution and mobility of 5-HT_(1A) tagged with EGFP can be monitored in the 5-HT_(1A)-EGFP stable PC12 cell line,which could be an excellent neuron-like experimental cell model for research of 5-HT_(1A) trafficking and signaling.