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Abstract Genetic changes in platelet serotonin receptors (5-HTR2A) impair the initial process of tissue repair, regardless of the triggering factor of the skin wound. Objective was to determine the prevalence of the 102T-C polymorphism in the 5-HTR2A gene in Brazilian patients with and without skin wounds. Cross-sectional case-control study, in which 100 patients were evaluated as Cases Group (subdivided into I-with Chronic Wound and II-with Acute Wound) and 100 individuals as Controls, of both genders. DNA was extracted from leukocytes of peripheral blood and the region that covers the polymorphism was amplified by the molecular techniques Polymerase Chain Reaction/Restriction Fragment Length Polymorphism. The TT genotype was significantly associated with the protective factor against alterations in the healing process of skin wounds (OR: 0.4833; 95%CI: 0.2704-0.8638; p<0.05) in the Control Group. The genotypic analysis between Cases Group (I-Chronic Wound and II-Acute Wound) determined that the TT genotype was significantly associated with the protection factor in Case II (OR: 0.3333; 95%CI: 0.1359-0.8177; p<.005) and the CC genotype was significantly associated with the chance to develop chronic ulcers in the Case I (OR: 6.667; 95%CI: 1.801-24.683; p<0.05). Patients with chronic skin wounds have a higher prevalence of the 102T-C polymorphism in the 5-HTR2A gene, which is associated to alterations in the healing process in this population. There are differences, at the molecular level, in patients, with and without these lesions, and the probable role of the serotonergic system in wound healing.
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OBJECTIVE To evaluate the correlation between 5-HTR1A gene C- 1019G polymorphism and the efficacy of antidepressants. METHODS PubMed，Embase，Cochrane Library ，CNKI，Wanfang database ，CBM and VIP database were searched for domestic and foreign literatures on the correlation between 5-HTR1A gene C- 1019G polymorphism and antidepressant efficacy. The retrieval time limit was from the inception to February 2022. According to different outcome measures of drug response，Stata 14.0 and RevMan 5.4 software were used for meta-analysis of efficacy group and remission group ，respectively. RESULTS A total of 18 literature were included. The combined results showed that among recessive gene model in valid group ， the correlation of 5-HTR1A gene C- 1019G polymorphism with the efficacy of antidepressants had statistically significance in Asian population（GG vs. CG+CC ，OR＝0.751，95％CI＝0.585-0.964，P＝0.024）. There was statistical significance in the correlation of 5-HTR1A gene C- 1019G polymorphism and the efficacy of antidepressants in China （GG vs. CG+CC ，OR＝0.677，95％CI＝ 0.508-0.901，P＝0.007）. There was no statistical significance in the correlation of 5-HTR1A gene C- 1019G polymorphism and the efficacy of antidepressants in remission group （P＞0.05）. CONCLUSIONS In the effective group ，5-HTR1A gene C- 1019G polymorphism is correlated with the efficacy of antidepressants in the Asian population and the Chinese population ；while in the remission group ，it is not proved that this polymorphism is correlated with the efficacy of antidepressants.
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Objective:To explore the effect of abdominal massage on the behavior of rats with neonatal hypoxia-ischemia and its mechanism.Methods:7-day-old SD rats were made as the HIBD model by the classical method of RICE and then the HIBD model rats were divided into the abdominal massage group and model group according to the random number table method, with 12 rats in each group, and 12 rats were selected as the normal group. The abdominal massage group was given abdominal massage 24 hours after the modeling, and the intervention continued for 28 days. Rats in each group underwent a balance beam test on the 7th, 14th, 21st, and 28th day of the intervention. After the intervention, HE staining was applied to observe the morphological structure of the hippocampal CA1 region of the rats; Quantitative Real-time PCR method was used to measure the serotonin receptor (5-HTR1A) in the hippocampus. The expression of cAMP, PKA and CREB in the hippocampus were measured by immunohistochemistry, and the expression of SYP protein was measured by Western blotting.Results:After the intervention, the cells in the hippocampal CA1 area of the model group were diffusely distributed, the number of neurons reduced, and the condition of inflammatory edema appeared; the cells in hippocampal CA1 area of the abdominal massage group were arranged clearly, and the condition of inflammatory edema has significantly improved; on the 21st and 28th day of the intervention, the balance beam test scores in the abdominal massage group significantly decreased ( P<0.05), and the relative expression of 5-HTR1A mRNA (1.18±0.08 vs. 0.77±0.04) in the abdominal massage group significantly increased ( P<0.05). The expression of cAMP (0.32±0.02 vs. 0.31±0.01), PKA (0.32±0.02 vs. 0.29±0.01),CREB (0.31±0.02 vs. 0.28±0.01) and SYP in the abdominal massage group significantly increased ( P<0.05). Conclusion:Abdominal massage could improve the behavior of neonatal hypoxic-ischemic rats, which may play a role on nerve repair by regulating 5-HTR1A/cAMP/PKA signaling pathway.
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AIM: To investigate the association of dopamine D2 receptor (DRD2) and 5-hydroxytryptamine 2A receptor (5-HTR2A) gene polymorphisms and their interactions with efficacy of olanzapine in treatment of schizophrenic patients. METHODS: A total of 147 schizophrenic patients who treated with olanzapine alone were recruited. The positive and negative symptom scale (PANSS) was used to evaluate the efficacy of drugs. According to PANSS reduction rate ≥50% and <50%, patients were divided into the effective group and the ineffective group. The gene polymorphisms of DRD2 (rs1799978, rs1800497) and 5-HTR2A (rs6311, rs6313) were detected by improved multiple ligase detection reaction (iMLDR). Multivariate Logistic regression analysis was used to analyze the correlation between genotypes and olanzapine efficacy, and multifactor dimensionality reduction (MDR) was used to analyze gene-gene interactions. RESULTS: There were significant differences in genotype and allele frequencies of rs1799978 and rs6313 between the effective group and the ineffective group (P<0.05), while there was no difference in genotype and allele frequencies of rs1800497 and rs6311 (P<0.05). Patients with GA and GG of rs1799978 locus were more effective than those with wild type AA when treated with olanzapine, and the ORs (95%CI) were 5.101 (1.118-23.267) and 6.051 (2.454-14.925), respectively. Patients with CT and CC of rs6313 locus were more effective than those with wild type TT when treated with olanzapine, and the ORs (95%CI) were 2.623 (1.054-6.528) and 3.412 (1.180-9.869), respectively. There was a interaction between the gene polymorphisms of rs1799978, rs1800497 and rs6313. The interaction model was the optimal gene-gene interaction model (P<0.05) with the verify sample accuracy rate of 0.727 3 and a cross-validation consistency of 10/10. CONCLUSION: The gene polymorphisms of DRD2 (rs1799978) and 5-HTR2A (rs6313) may be associated with efficacy of olanzapine in treatment of schizophrenic patients, and there is a interaction between DRD2 (rs1799978, rs1800497) and 5-HTR2A (rs6313) on the efficacy of olanzapine.
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Objective To investigate gene-gene interactions of suicidal behavior with single-nucleotide-polymorphism (SNP) in MAOA ,GAD1 and 5-HTR2C by multifactor dimensionality reduction .Methods For this case-control study ,six SNPs were captured in related genes and detected in blood samples obtained from 21 patients with suicidal behavior and 50 healthy individuals .The genotype frequency and allele frequency as well as the Hardy-Weinberg equilibrium (HWE) ,tests were performed and compared by plink software .The gene-gene interactions models were built by the MDR software .Results The HWE test for case group showed that rs3813928 rs518147 of 5-HTR2C gene was not in line with HWE ( P< 0 .05) .However ,the additive model analysis after adjustment by gender indicated that the polymorphism had a positive correlation with suicidal behavior in case group .The case and control groups differed significantly only in genotype frequencies of 5-HTR2C gene (χ2 =6 .18 , P=0 .04) .There was no significant difference in allele and genotype frequencies of the other genes ( P>0 .05) .The best combination model of MDR was rs5953210-rs769391 OR=20 .19 ,95% CI 4 .19-97 .38 , P<0 .01 ,with significant interaction . Conclusion The 5-HTR2C gene rs3813928 and rs518147 polymorphisms may play an important role in the susceptibility to suicidal behavior .The combination of MAOA with GAD1 has a significant interaction which may increase the risk of suicidal behavior .
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Objective To explore the effects of acupuncture on pruritic behaviors, expression of 5-HT neurons in medulla oblongata and 5-HTR2B on mice with chloroquine-induced pruritus; To discuss the mechanism of action of acupuncture in chloroquine-induced pruritus. Methods A non-histamine-dependent pruritus model was prepared by subcutaneous injection of chloroquine into the back of the neck. Forty C57B/6J mice were randomly divided into model-acupuncture group, model-non-acupuncture group, normal saline group and blank control group, with 10 mice in each group. After modeling, acupuncture was given in Xuehai, Quchi and Hegu on both sides. The plug and twist way was used to stimulate, once a day, three times. Model-non-acupuncture group received no acupuncture. Normal saline group received the neck injection of saline in the back. Blank control group received no treatment. Behavioral changes were observed, and immunofluorescence technique and Western blot were used to test the expression of 5-HT neurons and 5-HTR2B in medulla oblongata neurons. Results The number of scratches in model-acupuncture group and model-non-acupuncture group was obviously more than normal saline group and blank control group (P<0.05). The number of scratches in model-acupuncture group was lower than that of model-non-acupuncture group (P<0.05). The expression of 5-HT in medulla oblongata neurons was unclear in both normal saline group and blank control group. The expression of 5-HT neurons in medulla oblongata significantly increased in model group, which decreased after acupuncture. The expression of 5-HTR2B of model group was significant higher than normal saline group and blank control group (P<0.01). Compared with model-non-acupuncture group, the expression of 5-HTR2B in model-acupuncture group significant decreased (P<0.01). Conclusion Acupuncture can significantly inhibitscratching behaviors in mice induced by chloroquine, and the mechanism may be realized by decreasing the expression of 5-HT neurons and 5-HTR2B in medulla oblongata neurons.
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OBJECTIVE: Serotonin-1A receptors (5-HTR1A) is suggested to be involved in the etiology of several psychiatric disorders including panic disorder (PD). A few imaging studies have suggested the alterations of the cingulum bundle in PD. The objective of this study is to examine the structural changes of cingulum related to the 5-HTR1A polymorphism rs6295 in the patients with PD. METHODS: Thirty-two right-handed patients with PD [11 men, 21 women; 40.34+/-13.17 (mean+/-SD) age] who met the diagnostic criteria in Structured Clinical Interview for DSM-IV were examined by means of MRI at 3 Tesla. We divided the patients with PD into CC genotype group and non CC genotype group (GG/CG genotype group) of the 5-HTR1A rs6295 polymorphism to compare the cingulum white matter connectivity. RESULTS: Tract-based spatial statistics showed significantly increased fractional anisotropy (FA) values in cingulate gyrus process of left cingulum in 5-HTR1A CC genotype compared to GG/CG genotype in PD. Significant positive correlations were shown between the Albany Panic and Phobia Questionnaire (APPQ) interoceptive fear subscale scores, the Anxiety Sensitivity Inventory-Revised fear of publicly observable anxiety reaction subscale scores and FA values of cingulate gyrus process of left cingulum in 5-HTR1A rs6295 GG/CG genotype group. In CC genotype group, APPQ total, APPQ agoraphobia subscale and APPQ social phobia subscale scores also showed significant positive correlations with FA values of hippocampal process of right cingulum. CONCLUSION: This preliminary study suggests that 5-HTR1A polymorphism may be associated with the cingulum white matter connectivity in PD.
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Female , Humans , Male , Agoraphobia , Anisotropy , Anxiety , Diagnostic and Statistical Manual of Mental Disorders , Genotype , Gyrus Cinguli , Magnetic Resonance Imaging , Neuroimaging , Panic Disorder , Panic , Phobic Disorders , Surveys and QuestionnairesABSTRACT
Objective:To investigate the distribution of serotonin 5-HT2A and 5-HT7 receptors in different motoneuron populations in spinal Onuf’s nucleus of male rats,and their relationship with the central modulation of the urogenital functions.Methods:Ten adult SD rats(eight male rats and two female rats)were randomly divided into gender control group(n=4,include two male and two female rats)and retrograde tracing group(male rats,n=6).In gender control group,after the spinal L5~6 segments were removed and cut,sections were treated with 5-HT2A or 5-HT7 receptors immunohistochemical stain.In retrograde tracing group,recombinant pseudorabies virus(PRV-152 )were injected into right ischiocavernosus muscles(IC group;n=3)or right external urethral sphincter(EUS group;n=3),respectively.Four days after injection,the L5~6 segments were removed,cut,and treated with 5-HT2A or 5-HT7 receptors double-labeling immunofluorescence stain.Sections were observed by light microscopy or the laser confocal microscopy to detect the distribution of 5-HT2A、5-HT7 receptors in Onuf’s nucleus.Results:5-HT2A receptors immunoreactivity mainly located in the medial part of the dorsolateral nucleus(DLN)of Onuf’s nucleus,and 5-HT7 receptors mainly located in the lateral part of the DLN;5-HT2A and 5-HT7 receptors expression of male rats in Onuf’s nucleus were more dense than female rats.Immunofluorescence double-labeling detection exhibited that 5-HT2A receptors mainly distributed in surrounding motoneurons innervating the IC muscles,and 5-HT7 receptors mainly expressed in neurons innervating the EUS.Conclusion:5-HT2A and 5-HT7 receptors are heterogeneously distributed in different motoneurons of Onuf’s nucleus innervating different striated muscles.5-HT2A receptor might be preferentially involved in regulation of the sexual reflex,and the 5-HT7 receptor may be mainly participated in the micturition reflex.
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Objective To study the effect of 8Hz infrasound on the expression of 5-HTR of hippocampus and temporal cortex in rats. Methods SD rats were exposed to 8Hz, 90dB,100dB or 130dB infrasound, respectively for 2 hours daily. Then the rats' brains were taken and given stained immunohistochemically for (5-hydroxy tryptamine receptor,5-HTR). The content of 5-HTR in hippocampus and temporal cortex were detected under an optical microscope. Results The animals in the infrasound groups had less expression of 5-HTR in hippocampus and temporal cortex, and the least were at the 35th day for 90dB group and 100dB group and the 28th day for 130dB group (P
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Objective To study the effects of DHPs calcium antagonist Mn9202 and lacidipine on 5-HT、TH and 5-HTR of rat stomach fundus smooth muscle cells. Methods It's effects was investigated by using immunocytochemistry and image analysis of stom- ach fundus smooth muscle cells in culture and compared with cyprohetadine(antagonist of 5-HT). Results 5-HT、TH and 5-HTR im- munoreactive substances were existed in SFSMC. The results of image analysis indicated that the content of 5-HT. TH and 5-HTR were significantly lower when using Mn9202.lacidipine and cyprohetadine. Conclusion The results suggest that the rat stomach fundus smooth muscle cells possess 5-HT autocrine function, and DHPs calcium antagonist reduce the number of 5-HT receptor in the rat stomach fundus smooth muscle cells though the reduction of 5-HT sythesis, this results conform with cyprohetadine (antagonist of 5 - HT).
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Objective Studies on the changes of ? EP, 5-HT, 5-HTR immunoreactive cells in pancreatic islets during experimental gastric ulcer. Methods The immunohistochemical technique was used. Results The numerical densities on area of ? EP, 5-HT, 5-HTR cells in experimental gastric ulcer group were higher than control group on the 4day,10day after operation.The peak of the numerical densities on area of ? EP and 5-HT cells appeared on the 4th day, while the peak of 5-HTR cells as on the 10th day. Part of ? EP, 5-HT,5-HTR immunoreactive material were located in A or B cells neighbourly section. Conclusion The present work proved that the ? EP, 5-HT,5-HTR cells of pancreatic islets were directly or indirectly participated in the regulation balance of endocrine during the self-healing process of the experimental gastric ulcer and here we provided morphological evidence.;