Previous studies have indicated that the pathogenesis of amyotrophic lateral sclerosis(ALS) is closely linked to 5-hydroxytryptamine(5-HT).To investigate this further,we administered 5-HT receptor antagonists to SOD1*...Previous studies have indicated that the pathogenesis of amyotrophic lateral sclerosis(ALS) is closely linked to 5-hydroxytryptamine(5-HT).To investigate this further,we administered 5-HT receptor antagonists to SOD1*G93A transgenic(ALS mouse model) and wide-type mice.This involved intraperitoneal injections of either granisetron,piboserod,or ritanserin,which inhibit the 5-HT3,5-HT4,and 5-HT2 receptors,respectively.The transgenic mice were found to have fewer5-HT-positive cells in the spinal cord compared with wide-type mice.We found that the administration of granisetron reduced the body weight of the transgenic mice,while piboserod and ritanserin worsened the motor functioning,as assessed using a hanging wire test.However,none of the 5-HT receptor antagonists affected the disease progression.We analyzed the distribution and/or expression of TAR DNA binding protein 43(TDP-43) and superoxide dismutase 1 G93A(SOD1-G93A),which fo rm abnormal aggregates in ALS.We found that the expression of these proteins increased following the administration of all three 5-HT receptor antagonists.In addition,the disease-related mislocalization of TD P-43 to the cytoplasm increased markedly for all three drugs.In ce rtain anatomical regions,the 5-HT receptor antagonists also led to a marked increase in the number of astrocytes and microglia and a decrease in the number of neurons.These results indicate that 5-HT deficiency may play a role in the pathogenesis of amyotrophic lateral sclerosis by inducing the abnormal expression and/or distribution of TDP-43 and SOD1-G93A and by activating glial cells.5-HT co uld therefore be a potential therapeutic target for amyotrophic lateral sclerosis.展开更多
Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In...Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In this study,we found that 5-hydroxytryptamin receptor 3A subunit(HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice(an Alzheimer’s disease model) and patients with Alzheimer’s disease.To investigate whether HTR3A-positive interneurons are associated with the production of Aβ plaques,we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aβ plaques in the mouse model.Some amyloid precursor protein-positive or β-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aβ plaques were co-localized with HTR3A interneurons.These results suggest that HTR3A-positive interneurons may partially contribute to the generation of Aβ peptides.We treated 5.0-5.5-month-old model mice with tro pisetron,a HTR3 antagonist,for 8 consecutive weeks.We found that the cognitive deficit of mice was partially reversed,Aβ plaques and neuroinflammation we re remarkably reduced,the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice.These findings suggest that HTR3A interneurons partly contribute to generation of Aβ peptide at the initial stage of Alzheimer’s disease and inhibiting HTR3 partly reve rses the pathological changes of Alzheimer’s disease.展开更多
AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang(TXYF) improves dysfunction in an irritable bowel syndrome(IBS) rat model. METHODS: Thirty baby rats for IBS modeling were separated from mother rats(1...AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang(TXYF) improves dysfunction in an irritable bowel syndrome(IBS) rat model. METHODS: Thirty baby rats for IBS modeling were separated from mother rats(1 h per day) from days 8 to 21, and the rectum was expanded by angioplasty from days 8 to 12. Ten normal rats were used as normal controls. We examined the effects of TXYF on defection frequency, colonic transit function and smooth muscle contraction, and the expression of 5-hydroxytryptamine(5-HT) and substance P(SP) in colonic and hypothalamus tissues by Western blot and RT-PCT techniques in both normal rats and IBS model rats with characterized visceral hypersensitivity.in normal rats and 4.5 ± 1.58 in IBS model rats(P < 0.001). However, the defecation frequency was significantly decreased(3.0 ± 1.25 vs 4.5 ± 1.58, P < 0.05), while the time(in seconds) of colon transit function was significantly increased(256.88 ± 20.32 vs 93.36 ± 17.28, P < 0.001) in IBS + TXYF group rats than in IBS group rats. Increased colonic smooth muscle tension and contract frequency in IBS model rats were significantly decreased by administration of TXYF. Exogenous agonist stimulants increased spontaneous activity and elicited contractions of colon smooth muscle in IBS model rats, and all of these actions were significantly reduced by TXYF involving 5-HT and SP down-regulation. CONCLUSION: TXYF can modulate the activity of the enteric nervous system and alter 5-HT and SP activities, which may contribute to the symptoms of IBS.展开更多
Objective To investigate changes of 5-hydroxytryptamine (5-HT) and its synthesis rate-limiting enzyme tryp-tophan hydroxylase (TPH) in the ventral horn of spinal cord after exercise-induced fatigue, and to further...Objective To investigate changes of 5-hydroxytryptamine (5-HT) and its synthesis rate-limiting enzyme tryp-tophan hydroxylase (TPH) in the ventral horn of spinal cord after exercise-induced fatigue, and to further discuss the mecha- nism of exercise-induced central fatigue at spinal level. Methods Sixteen healthy adult Wistar rats were randomly divided into 2 groups: exercise-induced fatigue group and control group. Immunohistochemical staining for 5-HT and TPH in the ventral horn were performed and analysized quantitatively. The mean optic densities of 5-HT and TPH positive fibers or terminals were measured by computerized image analyzer. Results Both 5-HT and TPH positive fibers/terminals decreased in the exercise-induced fatigue group. The immunohistochemical staining was weaker and the mean optic densities decreased obviously in the fatigue group compared with those in the control group (P 〈 0.05). Conclusion 5-HT and TPH in the ventral horn of spinal cord might be involved in exercise-induced fatigue.展开更多
BACKGROUND: The orbitofrontal cortex (OFC) is a brain region closely associated with emotion. 5-hydroxytryptamine (5-HT) has been shown to be involved in human depression. OBJECTIVE: To investigate OFC actions a...BACKGROUND: The orbitofrontal cortex (OFC) is a brain region closely associated with emotion. 5-hydroxytryptamine (5-HT) has been shown to be involved in human depression. OBJECTIVE: To investigate OFC actions and mechanisms of 5-HT and 5-HT1A receptor (5-HT1AR) in stress-induced depression.DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at Laboratory of Neurobiology, College of Life Science, Shaanxi Normal University between May 2006 and March 2008. MATERIALS: 5-HT, p-chlorophenylalanine (PCPA, an inhibitor to tryptophan hydroxylase) and spiperone (5-HT1AR antagonist) were provided by Sigma, USA; rabbit anti-rat 5-HT1AR antibody was provided by Tianjin Haoyang Biological Manufacture. METHODS: A total of 40 male Sprague Dawley rats, aged 3 months, were randomly divided into five groups: control, model, 5-HT, spiperone + 5-HT, and PCPA, with 8 rats in each group. Except for control group, rats in the other four groups were used to establish depression models by forced swimming for 15 minutes. At 30 minutes before forced swimming test, 0.5 pL of 5-HT (12.5 pg/pL), PCPA (20 pg/pL), spiperone (1.3 pg/pL) + 5-HT (12.5 pg/pL, 10 minutes later), and saline were respectively injected into the OFC of 5-HT, PCPA, spiperone + 5-HT, and model groups, respectively. The control group received a saline microinjection into the OFC.MAIN OUTCOME MEASURES: Forced swimming and open field tests were employed to measure animal behaviors, and immunohistochemistry was used to analyze 5-HT1AR expression in the OFC, cingulate cortex, and piriform cortex. RESULTS: (1) Compared with the model group, 5-HT microinjection into the OFC prominently reduced immobility time in the forced swimming test and rearing in open field test (P 〈 0.05); locomotion and grooming in open field test were increased, although there was no significance (P 〉 0.05). Furthermore, following PCPA microinjection into the OFC (PCPA + forced swimming stress), immobility time in forced swimming test increased dramatically (P〈 0.01), locomotion and rearing in open field test declined (P〈 0.05 and P 〈 0.01, respectively). Compared with the 5-HT group, 5-HT1AR antagonist (spiperone + 5-HT + forced swimming stress) increased immobility time in forced swimming test (P 〈 0.01), but decreased locomotion, rearing, and grooming in open field test. (2) Forced swimming stress markedly elevated 5-HT1AR expression in OFC, cingulate cortex, and piriform cortex (P〈 0.05 or P〈 0.01). CONCLUSION: 5-HT improved stress-induced depression, and 5-HT anti-depression effects are primarily achieved via 5-HT1AR. Stress-induced up regulation of 5-HT1AR expression might be a compensatory mechanism for decreased 5-HT expression.展开更多
Objective:The present study aimed to investigate the effect of seasonal variation on neurotransmitter release in the hippocampus of normal rats and rats with pineal excision.Methods:Two time points,the summer and wint...Objective:The present study aimed to investigate the effect of seasonal variation on neurotransmitter release in the hippocampus of normal rats and rats with pineal excision.Methods:Two time points,the summer and winter solstice,which are the longest and shortest days of the year,respectively,were selected.Male Spraguee Dawley rats that underwent a sham operation without pineal excision were included as a control group.The concentrations of 5-hydroxytryptamine(5-HT)andγ-aminobutyric acid(GABA)were determined by radioimmunoassays and enzyme-linked immunosorbent assays,respectively.Results:In the winter,the 5-HT and GABA levels in normal rats exhibited a significant difference compared with those in the operation group(P<.01).A difference was also noted in GABA levels between the normal group and the sham operation group(P<.05).The concentrations of 5-HT and GABA in the hippocampal tissues of the normal group exhibited a seasonal rhythm consisting of elevation during the summer and reduction during the winter(P<.01),while the GABA levels in the sham operation group exhibited a significant difference,with elevation during the summer and reduction during the winter(P<.01).In the operation group,GABA showed the same trend(P<.01).Conclusion:The seasonal rhythm of neurotransmitter secretion by the hippocampus(5-HT and GABA)consisted of elevation during the summer and reduction during the winter.During the winter,the pineal gland exhibited a reverse regulatory effect on the secretion of 5-HT and GABA in the hippocampus,and it exhibited seasonal selectivity with regard to the regulation of 5-HT.展开更多
5-hydroxytryptamine contributes to the control of activities of the dilator muscle in the upper respiratory tract, and is derived from the raphe nuclei, in which the habenular nucleus exerts a sustaJned inhibitory eff...5-hydroxytryptamine contributes to the control of activities of the dilator muscle in the upper respiratory tract, and is derived from the raphe nuclei, in which the habenular nucleus exerts a sustaJned inhibitory effect. In the present study, respiratory motion curve of the genJoglossus muscle and peripheral 5-hydroxytryptamine changes were observed following L-glutamate stimulation of the habenular nucleus of adult Wistar rats. Results showed that the rats had apnea and decreased plasma 5-hydroxytryptamine content after the neurons in habenular nucleus were excited. Genioglossus muscle electromyogram amplitude and integral were significantly reduced. The genioglossus myoelectric activity and respiratory motion curve were similar to obstructive sleep apnea syndrome, thus confirming that the habenular nucleus is the key nucleus involved in the pathogenesis of obstructive sleep apnea syndrome, and is the primary regulated center in the raphe nuclei. Stimulation of the habenular nucleus may suppress 5-hydroxytryptamine release and result in apnea, which is similar to obstructive sleep apnea syndrome.展开更多
In the present study, electrical stimulation to the rat insular cortex induced apnea or respiratory disturbance, reduced amplitude of genioglossal electromyogram, and decreased electromyogram integrals. In addition, a...In the present study, electrical stimulation to the rat insular cortex induced apnea or respiratory disturbance, reduced amplitude of genioglossal electromyogram, and decreased electromyogram integrals. In addition, arterial blood gas analysis showed arterial blood acidosis, reduced pH values, increased alkali reserve negative values, decreased peripheral blood 5-hydroxytryptamine content, and increased 5-hydroxytryptamine expression in cerebellar Purkinje cells. Following lidocaine injection to block the habenular nucleus, abnormalities in breath, genioglossal electromyogram, and blood gas values disappeared, and peripheral blood 5-hydroxytryptamine content returned to levels prior to electric stimulation. However, 5-hydroxytryptamine expression in cerebellar Purkinje cells remained high. The results suggested that 5-hydroxytryptamine expression in Purkinje cells did not correlate with ventilation function involving insular cortex and habenular nucleus.展开更多
[ Objective] To find the rule of 5-hydroxytryptamine (5-HT) synthesis and metabolism in peripheral blood of suckling piglets with aging. [ Method ] All of 15 British Large White pigs at 0, 5 and 15 d of age were sel...[ Objective] To find the rule of 5-hydroxytryptamine (5-HT) synthesis and metabolism in peripheral blood of suckling piglets with aging. [ Method ] All of 15 British Large White pigs at 0, 5 and 15 d of age were selected as experimental animals, and their serumal concentrations of L- tryptophan (L-Trp), 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in peripheral circulatory system were determined synchronously by reversed- phase high-performance liquid chromatography method with UV. [ Result] The concentration of L-Trp was (16. 92 ± 1.74) iJmol/L at birth, (59.94 ±10.88) iJmol/L at 5 d of age and (70.42± 6.48) μmol/L at 15 d of age. The concentration of 5-HT was ( 12.85 ± 1.79) iJmol/L at birth, (4.81 ±2.05) ijmol/L at 5 d of age and (5.49±1.09) μmol/L at 15 d of age. While 5-HIAA, the metabolic product of 5-HT, was not detected at all the samples selected. [ Conclusion] The L-Trp concentration of suckling piglets increase significantly with aging ( P 〈0. 05). While the concentra- tion of 5-HT and the conversion ratio of L-Trp to 5-HT are both highest at birth (P〈0.05) and keep stable at 5 and 15 d of age.展开更多
In the first and second parts of this study,5-hydroxytryptamine(5HT)receptors,including 5-HT3 and 5-HT4 with the highest expression level,were found in clasp and sling fibres of the lower esophageal sphincter(LES).Spe...In the first and second parts of this study,5-hydroxytryptamine(5HT)receptors,including 5-HT3 and 5-HT4 with the highest expression level,were found in clasp and sling fibres of the lower esophageal sphincter(LES).Specific 5-HT3 and 5-HT4 receptor agonists can induce the contraction effect of clasp and sling fibres of the LES while specific 5-HT7 receptor agonists showed no effects.In the study of this part,the in-vitro muscle tension measurement technology and EFS methods were used to detect the effect of the selective 5-HT receptor antagonist on the clasp and sling fibres of the in-vitro LES under the electrical field stimulation(EFS),and further to ensure the effect of 5-HT receptor in the LES neuroregulatory pathway,and deeply explore the effect of 5-HT receptor in the systolic and diastolic function regulation of the LES.展开更多
We evaluated the genotypes of the serotonin transporter gene (5-HTT) in patients with premature ejaculation (PE) to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the ...We evaluated the genotypes of the serotonin transporter gene (5-HTT) in patients with premature ejaculation (PE) to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the patient subgroups. A total of 70 PE patients and 70 controls were included in this study. All men were heterosexual, had no other disorders and were either married or in a stable relationship. PE was defined as ejaculation that occurred within 1 min of vaginal intromission. Genomic DNA from patients and controls was analyzed using polymerase chain reaction, and allelic variations of the promoter region of the serotonin transporter gene (5-HTTLPR) were determined. The 5-HTTLPR (serotonin transporter promoter gene) genotypes in PE patients vs. controls were distributed as follows: L/L 16% vs. 17%, L/S 30% vs. 53% and S/S 54% vs. 28%. We examined the haplotype analysis for three polymorphisms of the 5-HTTLPR gene: LL, LS and SS. The appropriateness of the allele frequencies in the 5-HTTLPR gene was analyzed by the Hardy-Weinberg equilibrium using the Z-test. The short (S) allele of the 5-HTTLPR gene was significantly more frequent in PE patients than in controls (P 〈 0.05). We suggest that the 5-HTTLPR gene plays a role in the pathophysiology of all primary PE cases. Further studies are needed to evaluate the relationship between 5-HTTLPR gene polymorphism and patient subgroup (such as primary and secondary PE) responses to selective serotonin reuptake inhibitors as well as ethnic differences.展开更多
5-Hydroxytryptamine(5-HT)type 3 receptor(5-HT_(3)R)is the only type of ligand-gated ion channel in the 5-HT receptor family.Through the high permeability of Na+,K+,and Ca2+and activation of subsequent voltage-gated ca...5-Hydroxytryptamine(5-HT)type 3 receptor(5-HT_(3)R)is the only type of ligand-gated ion channel in the 5-HT receptor family.Through the high permeability of Na+,K+,and Ca2+and activation of subsequent voltage-gated calcium channels(VGCCs),5-HT_(3)R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system(CNS).5-HT_(3)Rs are widely expressed in the medial prefrontal cortex(mPFC),amygdala(AMYG),hippocampus(HIP),periaqueductal gray(PAG),and other brain regions closely associated with anxiety reactions.They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions.5-HT_(3)Rs mediate the activation of the cholecystokinin(CCK)system in the AMYG,and theγ-aminobutyric acid(GABA)“disinhibition”mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons(IINs).In contrast,a 5-HT_(3)R-induced GABA“disinhibition”mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects.5-HT_(2)R-mediated regulation of anxiety reactions are also activated by 5-HT_(3)R-activated 5-HT release in the HIP and PAG.This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT_(3)Rs.However,given the circuit specific modulation of 5-HT_(3)Rs on emotion,systemic use of 5-HT_(3)R agonism or antagonism alone seems unlikely to remedy anxiety,which deeply hinders the current clinical application of 5-HT_(3)R drugs.Therefore,the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.展开更多
BACKGROUND:Motoneurons from the Onuf’s nucleus of the spinal cord, which innervate the striated muscle of the pelvic floor, play an important role in erection, ejaculation, and urine control. Serotonin (5-hydroxytr...BACKGROUND:Motoneurons from the Onuf’s nucleus of the spinal cord, which innervate the striated muscle of the pelvic floor, play an important role in erection, ejaculation, and urine control. Serotonin (5-hydroxytryptamine, 5-HT) regulates motoneuron activity from the Onuf’s nucleus of the spinal cord. However, few studies exist that describe 5-HT receptor distribution in the Onuf’s nucleus. In addition, the nature of the effects of 5-HT receptor on the innervating striated muscle of the pelvic floor is controversial. OBJECTIVE: To investigate the distribution of serotonin 5-HT2A and 5-HT7 receptors in motoneurons of Onuf’s nucleus in the spinal cord of male rats, and to analyze the relationship of 5-HT2A and 5-HT7 receptor to central modulation of urogenital function. DESIGN, TIME AND SETTING: The neural morphology experiment was performed at the Ultramicro-structure Laboratory of Reproductive Medicine, Basic Medical College, Chongqing Medical University, China from April to December 2007. MATERIALS: Ten adult, Sprague Dawley rats (eight males and two females) were randomly divided into gender control group (n = 4, 50% male and 50% female) and a retrograde tracing group (n = 6, 100% male) Recombinant pseudorabies virus (PRV-152) was provided by Professor LW Enquist from Princeton University, USA. Rabbit anti-5-HT2A and 5-HT7 receptor antibodies were purchased from Diasorin, France. METHODS: In the gender control group, the spinal L5-6 segments were harvested, sliced, and then incubate antibodies specific against 5-HT2A or 5-HT7 receptors for immunohistochemical staining. In the retrograde tracing group, PRV-152 was separately injected into the right ischiocavernosus (ischiocavernosus subgroup, n = 3) and the right external urethral sphincter (external urethral sphincter subgroup, n = 3). Four days after injection, L5-6 segments were harvested, sliced, and incubated with antibodies specific against 5-HT2A or 5-HT7 receptors for double-labeling immunofluorescence staining. MAIN OUTCOME MEASURES: Distribution analysis of 5-HT2A and 5-HT7 receptors in Onuf’s nucleus utilizing optical or laser confocal microscopy. RESULTS: 5-HT2A receptor immunoreactivity was revealed primarily in the medial region of the dorsolateral nucleus of Onuf’s nucleus. 5-HT7 receptor expression was observed in the lateral part of the dorso-lateral nucleus. 5-HT2A and 5-HT7 receptor expressions in the Onuf’s nucleus were significantly greater in male rats, compared to female rats. Double-labeling immunofluorescence demonstrated that 5-HT2A recepto were distributed primarily in the surrounding motoneurons innervating the ischiocavernosus, and 5-HT7 receptors were primarily expressed in motoneurons innervating the external urethral sphincter. CONCLUSION: Motoneurons innervating the ischiocavernosus and external urethral sphincter are located primarily in the medial and lateral region of the dorsolateral nucleus of L5-6 segments. The 5-HT2A receptor-innervating ischiocavernosus may be preferentially involved in the regulation of sexual reflex, and the 5-HT7 receptor-innervating external urethral sphincter may mainly join in regulating micturition reflex.展开更多
<b><span style="font-family:Verdana;">Background:</span></b><span style="font-family:""><span style="font-family:Verdana;"> It is not well analyze...<b><span style="font-family:Verdana;">Background:</span></b><span style="font-family:""><span style="font-family:Verdana;"> It is not well analyzed whether there are differences in plasma levels of tryptophan (TRP) metabolites between healthy control people (HC) and patients of major monopolar depression (MMD). </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> Ultra high-speed </span></span><span style="font-family:""><span style="font-family:Verdana;">liquid chromatography/mass spectrometry has been used for the simultaneous determination of plasma levels of tryptophan metabolites in depressive </span><span><span style="font-family:Verdana;">patients. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> There are no significant differences between plasma levels of TRP between HC and MMD. Plasma levels of TRP of HC are higher in young men, young women, old men, and old women in this order. Serotonin (5-HT) levels are higher in MMD than HC. Plasma levels of 5-HIAA of HC are also higher than those of patients of MMD. Plasma levels of kynurenine (KYN) of healthy old men and old women are higher than those of young men and old women. Plasma levels of KYN are higher in old women and young men of MMD than those of HC. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> Plasma levels of 5-HT are higher in patients of MMD than those of HC, which may suggest that use of drugs inhibiting the 5-HT transportation may increase plasma levels of 5-HT in MMD.展开更多
目的评价单独使用磷酸二酯酶-5型(PDE5)抑制剂或联合五羟色胺再摄取抑制剂(SSRIs)对比单独应用SSRIs治疗勃起功能障碍(ED)与早泄(PE)共病的疗效与安全性。方法检索下述网站:知网、PubMed、Web of Science、Embase、万方、维普数据库、...目的评价单独使用磷酸二酯酶-5型(PDE5)抑制剂或联合五羟色胺再摄取抑制剂(SSRIs)对比单独应用SSRIs治疗勃起功能障碍(ED)与早泄(PE)共病的疗效与安全性。方法检索下述网站:知网、PubMed、Web of Science、Embase、万方、维普数据库、中国生物医学文献服务系统、中华医学期刊,自建库起至2022年11月,单独使用PDE5抑制剂或联合SSRIs对比单独应用SSRIs治疗ED与PE共病的随机对照试验,用Revman 5.4.1软件分析阴道内射精潜伏期(IELT)、国际勃起功能指数5项问卷(IIEF-5)评分及不良反应率。结果最终纳入文献9篇,涉及793例患者。Meta分析显示:与单独应用SSRIs治疗ED与PE共病相比,单独使用PDE5抑制剂或联合SSRIs治疗后患者IELT更高[MD=1.99,95%CI(1.51~2.46),P<0.001]、IIEF-5评分更高[MD=4.61,95%CI(3.68~5.55),P<0.001],不良反应无统计学差异[RR=0.99,95%CI(0.74~1.31),P=0.92]。结论治疗ED与PE共病患者时,应优先治疗ED或同时治疗ED和PE,在ED和PE方面都能获得更好的治疗效果,同时不良反应也没有增加。展开更多
Serotonin is one of the significant signaling molecules used by several neural systems in the gut and brain. This study aimed to develop a novel and potent tracer for targeting, detecting, and imaging serotonin recept...Serotonin is one of the significant signaling molecules used by several neural systems in the gut and brain. This study aimed to develop a novel and potent tracer for targeting, detecting, and imaging serotonin receptors(5-HTRs), which is a promising tool in the determination of the receptor’s function and relationship with the diseases related to serotonin and its receptor dysfunction. Serotonin was effectively labeled via a direct electrophilic substitutional reaction using an oxidizing agent such as iodogen with 125I in a neutral medium, and 125I-serotonin was achieved with a maximum labeling yield of 91 ± 0.63% with in vitro stability up to 24 h. Molecular modeling was conducted to signify 125I-serotonin structure and confirm that the radiolabeling process did not affect serotonin binding ability to its receptors. Biodistribution studies show that the maximum gastro intestinal tract uptake of 125I-serotonin was 17.8 ± 0.93% ID/organ after 30 min postinjection and the tracer’s ability to pass the blood–brain barrier. Thus, 125I-serotonin is a promising single photon emission computed tomography tracer in the detection of 5 HTRs.展开更多
The present study examines the effects of serotonin (5-HT) 1A receptor ligands on humoral im-mune response in two rat lines selected for over 75 generations for the enhancement or elimination of aggression. Activation...The present study examines the effects of serotonin (5-HT) 1A receptor ligands on humoral im-mune response in two rat lines selected for over 75 generations for the enhancement or elimination of aggression. Activation of presynaptic 5-HT1A receptors with a low dose of the selective 5-HT1A receptor agonist 8-OH-DPAT (0.1 mg/kg) or the blockade of postsynaptic 5-HT1A receptors with the antagonist WAY-100635 (1.0 mg/kg) did not affect the numbers of IgM-antibody forming cells (IgM-AFC) in the spleen of highly aggressive rats, which were characterized by higher immune responsiveness compared to nonaggressive line. On the other hand, the same doses of 8-OH-DPAT and WAY-100635, as well as a higher dose of 8-OH-DPAT (1.0 mg/kg), which is known to activate postsynaptic 5-HT1A receptors, produce immunostimulation in nonaggressive rats. However, only the highest dose of 8-OH-DPAT (5.0 mg/kg) was able to cause immunosuppression in nonaggressive rats that was mainly dependent on stimulation of postsynaptic 5-HT1A receptors. In contrast to nonaggressive rats, the dose of 1.0 mg/kg 8-OH-DPAT was sufficient to produce a decrease in the numbers of IgM-AFC in highly aggressive rats. Thus, pharmacological activation of pre- and postsynaptic 5-HT1A receptors, as well as the blockade of postsynaptic 5-HT1A receptors, produced different effects on the immune response in two lines of rats selected for high level of aggression or its absence. These data may have implications for more efficient treatments of a number of mental disorders associated with abnormal aggression.展开更多
In our report, the values of whole blood serotonin (5-HT) in 87 apudoma patients (diagnosed by operation and pathology) were summarized. Among them, the levels of urinary 5-hydroxyindole-3-acetic acid (5-HIAA) of 44 p...In our report, the values of whole blood serotonin (5-HT) in 87 apudoma patients (diagnosed by operation and pathology) were summarized. Among them, the levels of urinary 5-hydroxyindole-3-acetic acid (5-HIAA) of 44 patients were also tested. The results showed that both parametres of apudoma patients were higher than those of non-apudoma, post-operative patients of apudoma as well as the normal. The increasing extent of the levels of whole blood 5-HT and urinary 5-HIAA in small intestinal carcihoid was the most obvious one but that of rectum was not. The referable diagnostic values suggested were: 5-HT>130 ng ml, 5-HIAA>30 mg/ 24 hours.展开更多
基金supported by the National Natural Science Foundation of China,Nos.30560042,81160161,8136019882160255+2 种基金Education Department of Jiangxi Province,Nos.GJJ13198 and GJJ170021Jiangxi Provincial Department of Science and Technology,Nos.20142BBG70062,20171 BAB215022,20192BAB205043Health and Family Planning Commission of Jiangxi Province,No.20181019 (all to RSX)。
文摘Previous studies have indicated that the pathogenesis of amyotrophic lateral sclerosis(ALS) is closely linked to 5-hydroxytryptamine(5-HT).To investigate this further,we administered 5-HT receptor antagonists to SOD1*G93A transgenic(ALS mouse model) and wide-type mice.This involved intraperitoneal injections of either granisetron,piboserod,or ritanserin,which inhibit the 5-HT3,5-HT4,and 5-HT2 receptors,respectively.The transgenic mice were found to have fewer5-HT-positive cells in the spinal cord compared with wide-type mice.We found that the administration of granisetron reduced the body weight of the transgenic mice,while piboserod and ritanserin worsened the motor functioning,as assessed using a hanging wire test.However,none of the 5-HT receptor antagonists affected the disease progression.We analyzed the distribution and/or expression of TAR DNA binding protein 43(TDP-43) and superoxide dismutase 1 G93A(SOD1-G93A),which fo rm abnormal aggregates in ALS.We found that the expression of these proteins increased following the administration of all three 5-HT receptor antagonists.In addition,the disease-related mislocalization of TD P-43 to the cytoplasm increased markedly for all three drugs.In ce rtain anatomical regions,the 5-HT receptor antagonists also led to a marked increase in the number of astrocytes and microglia and a decrease in the number of neurons.These results indicate that 5-HT deficiency may play a role in the pathogenesis of amyotrophic lateral sclerosis by inducing the abnormal expression and/or distribution of TDP-43 and SOD1-G93A and by activating glial cells.5-HT co uld therefore be a potential therapeutic target for amyotrophic lateral sclerosis.
基金supported by the Notional Natural Science Foundation of China,Nos.81371213 and 8107098 7the Natural Science Foundation of Shanghai,No.21ZR1468400 (all to QLY)。
文摘Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In this study,we found that 5-hydroxytryptamin receptor 3A subunit(HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice(an Alzheimer’s disease model) and patients with Alzheimer’s disease.To investigate whether HTR3A-positive interneurons are associated with the production of Aβ plaques,we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aβ plaques in the mouse model.Some amyloid precursor protein-positive or β-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aβ plaques were co-localized with HTR3A interneurons.These results suggest that HTR3A-positive interneurons may partially contribute to the generation of Aβ peptides.We treated 5.0-5.5-month-old model mice with tro pisetron,a HTR3 antagonist,for 8 consecutive weeks.We found that the cognitive deficit of mice was partially reversed,Aβ plaques and neuroinflammation we re remarkably reduced,the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice.These findings suggest that HTR3A interneurons partly contribute to generation of Aβ peptide at the initial stage of Alzheimer’s disease and inhibiting HTR3 partly reve rses the pathological changes of Alzheimer’s disease.
基金Supported by National Education Department"ChunHui Plan"Research Projects,No.Z2010021China Postdoctoral Science Foundation Project,No.2013M531079+2 种基金Heilongjiang Postdoctoral Funding Project,No.LBH-Z12246Heilongjiang Education Department Scientific Research Project,No.12521502excellent Innovative Talents Support Program Funding of Heilongjiang University of Chinese Medicine(Outstanding Young Academic Leaders),No.051217
文摘AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang(TXYF) improves dysfunction in an irritable bowel syndrome(IBS) rat model. METHODS: Thirty baby rats for IBS modeling were separated from mother rats(1 h per day) from days 8 to 21, and the rectum was expanded by angioplasty from days 8 to 12. Ten normal rats were used as normal controls. We examined the effects of TXYF on defection frequency, colonic transit function and smooth muscle contraction, and the expression of 5-hydroxytryptamine(5-HT) and substance P(SP) in colonic and hypothalamus tissues by Western blot and RT-PCT techniques in both normal rats and IBS model rats with characterized visceral hypersensitivity.in normal rats and 4.5 ± 1.58 in IBS model rats(P < 0.001). However, the defecation frequency was significantly decreased(3.0 ± 1.25 vs 4.5 ± 1.58, P < 0.05), while the time(in seconds) of colon transit function was significantly increased(256.88 ± 20.32 vs 93.36 ± 17.28, P < 0.001) in IBS + TXYF group rats than in IBS group rats. Increased colonic smooth muscle tension and contract frequency in IBS model rats were significantly decreased by administration of TXYF. Exogenous agonist stimulants increased spontaneous activity and elicited contractions of colon smooth muscle in IBS model rats, and all of these actions were significantly reduced by TXYF involving 5-HT and SP down-regulation. CONCLUSION: TXYF can modulate the activity of the enteric nervous system and alter 5-HT and SP activities, which may contribute to the symptoms of IBS.
文摘Objective To investigate changes of 5-hydroxytryptamine (5-HT) and its synthesis rate-limiting enzyme tryp-tophan hydroxylase (TPH) in the ventral horn of spinal cord after exercise-induced fatigue, and to further discuss the mecha- nism of exercise-induced central fatigue at spinal level. Methods Sixteen healthy adult Wistar rats were randomly divided into 2 groups: exercise-induced fatigue group and control group. Immunohistochemical staining for 5-HT and TPH in the ventral horn were performed and analysized quantitatively. The mean optic densities of 5-HT and TPH positive fibers or terminals were measured by computerized image analyzer. Results Both 5-HT and TPH positive fibers/terminals decreased in the exercise-induced fatigue group. The immunohistochemical staining was weaker and the mean optic densities decreased obviously in the fatigue group compared with those in the control group (P 〈 0.05). Conclusion 5-HT and TPH in the ventral horn of spinal cord might be involved in exercise-induced fatigue.
基金the Natural Science Foundation of Shaanxi Province,No. 2006C240
文摘BACKGROUND: The orbitofrontal cortex (OFC) is a brain region closely associated with emotion. 5-hydroxytryptamine (5-HT) has been shown to be involved in human depression. OBJECTIVE: To investigate OFC actions and mechanisms of 5-HT and 5-HT1A receptor (5-HT1AR) in stress-induced depression.DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at Laboratory of Neurobiology, College of Life Science, Shaanxi Normal University between May 2006 and March 2008. MATERIALS: 5-HT, p-chlorophenylalanine (PCPA, an inhibitor to tryptophan hydroxylase) and spiperone (5-HT1AR antagonist) were provided by Sigma, USA; rabbit anti-rat 5-HT1AR antibody was provided by Tianjin Haoyang Biological Manufacture. METHODS: A total of 40 male Sprague Dawley rats, aged 3 months, were randomly divided into five groups: control, model, 5-HT, spiperone + 5-HT, and PCPA, with 8 rats in each group. Except for control group, rats in the other four groups were used to establish depression models by forced swimming for 15 minutes. At 30 minutes before forced swimming test, 0.5 pL of 5-HT (12.5 pg/pL), PCPA (20 pg/pL), spiperone (1.3 pg/pL) + 5-HT (12.5 pg/pL, 10 minutes later), and saline were respectively injected into the OFC of 5-HT, PCPA, spiperone + 5-HT, and model groups, respectively. The control group received a saline microinjection into the OFC.MAIN OUTCOME MEASURES: Forced swimming and open field tests were employed to measure animal behaviors, and immunohistochemistry was used to analyze 5-HT1AR expression in the OFC, cingulate cortex, and piriform cortex. RESULTS: (1) Compared with the model group, 5-HT microinjection into the OFC prominently reduced immobility time in the forced swimming test and rearing in open field test (P 〈 0.05); locomotion and grooming in open field test were increased, although there was no significance (P 〉 0.05). Furthermore, following PCPA microinjection into the OFC (PCPA + forced swimming stress), immobility time in forced swimming test increased dramatically (P〈 0.01), locomotion and rearing in open field test declined (P〈 0.05 and P 〈 0.01, respectively). Compared with the 5-HT group, 5-HT1AR antagonist (spiperone + 5-HT + forced swimming stress) increased immobility time in forced swimming test (P 〈 0.01), but decreased locomotion, rearing, and grooming in open field test. (2) Forced swimming stress markedly elevated 5-HT1AR expression in OFC, cingulate cortex, and piriform cortex (P〈 0.05 or P〈 0.01). CONCLUSION: 5-HT improved stress-induced depression, and 5-HT anti-depression effects are primarily achieved via 5-HT1AR. Stress-induced up regulation of 5-HT1AR expression might be a compensatory mechanism for decreased 5-HT expression.
基金the National Natural Science Foundation of China(81774162)。
文摘Objective:The present study aimed to investigate the effect of seasonal variation on neurotransmitter release in the hippocampus of normal rats and rats with pineal excision.Methods:Two time points,the summer and winter solstice,which are the longest and shortest days of the year,respectively,were selected.Male Spraguee Dawley rats that underwent a sham operation without pineal excision were included as a control group.The concentrations of 5-hydroxytryptamine(5-HT)andγ-aminobutyric acid(GABA)were determined by radioimmunoassays and enzyme-linked immunosorbent assays,respectively.Results:In the winter,the 5-HT and GABA levels in normal rats exhibited a significant difference compared with those in the operation group(P<.01).A difference was also noted in GABA levels between the normal group and the sham operation group(P<.05).The concentrations of 5-HT and GABA in the hippocampal tissues of the normal group exhibited a seasonal rhythm consisting of elevation during the summer and reduction during the winter(P<.01),while the GABA levels in the sham operation group exhibited a significant difference,with elevation during the summer and reduction during the winter(P<.01).In the operation group,GABA showed the same trend(P<.01).Conclusion:The seasonal rhythm of neurotransmitter secretion by the hippocampus(5-HT and GABA)consisted of elevation during the summer and reduction during the winter.During the winter,the pineal gland exhibited a reverse regulatory effect on the secretion of 5-HT and GABA in the hippocampus,and it exhibited seasonal selectivity with regard to the regulation of 5-HT.
基金the National Natural Science Foundation of China, No. 30270502
文摘5-hydroxytryptamine contributes to the control of activities of the dilator muscle in the upper respiratory tract, and is derived from the raphe nuclei, in which the habenular nucleus exerts a sustaJned inhibitory effect. In the present study, respiratory motion curve of the genJoglossus muscle and peripheral 5-hydroxytryptamine changes were observed following L-glutamate stimulation of the habenular nucleus of adult Wistar rats. Results showed that the rats had apnea and decreased plasma 5-hydroxytryptamine content after the neurons in habenular nucleus were excited. Genioglossus muscle electromyogram amplitude and integral were significantly reduced. The genioglossus myoelectric activity and respiratory motion curve were similar to obstructive sleep apnea syndrome, thus confirming that the habenular nucleus is the key nucleus involved in the pathogenesis of obstructive sleep apnea syndrome, and is the primary regulated center in the raphe nuclei. Stimulation of the habenular nucleus may suppress 5-hydroxytryptamine release and result in apnea, which is similar to obstructive sleep apnea syndrome.
基金supported by the National Natural Science Foundation of China, No. 30270502
文摘In the present study, electrical stimulation to the rat insular cortex induced apnea or respiratory disturbance, reduced amplitude of genioglossal electromyogram, and decreased electromyogram integrals. In addition, arterial blood gas analysis showed arterial blood acidosis, reduced pH values, increased alkali reserve negative values, decreased peripheral blood 5-hydroxytryptamine content, and increased 5-hydroxytryptamine expression in cerebellar Purkinje cells. Following lidocaine injection to block the habenular nucleus, abnormalities in breath, genioglossal electromyogram, and blood gas values disappeared, and peripheral blood 5-hydroxytryptamine content returned to levels prior to electric stimulation. However, 5-hydroxytryptamine expression in cerebellar Purkinje cells remained high. The results suggested that 5-hydroxytryptamine expression in Purkinje cells did not correlate with ventilation function involving insular cortex and habenular nucleus.
基金funding from " Eleventh Five-Year" National Science and Technology Support Program of China (2007BAD86B-06)
文摘[ Objective] To find the rule of 5-hydroxytryptamine (5-HT) synthesis and metabolism in peripheral blood of suckling piglets with aging. [ Method ] All of 15 British Large White pigs at 0, 5 and 15 d of age were selected as experimental animals, and their serumal concentrations of L- tryptophan (L-Trp), 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in peripheral circulatory system were determined synchronously by reversed- phase high-performance liquid chromatography method with UV. [ Result] The concentration of L-Trp was (16. 92 ± 1.74) iJmol/L at birth, (59.94 ±10.88) iJmol/L at 5 d of age and (70.42± 6.48) μmol/L at 15 d of age. The concentration of 5-HT was ( 12.85 ± 1.79) iJmol/L at birth, (4.81 ±2.05) ijmol/L at 5 d of age and (5.49±1.09) μmol/L at 15 d of age. While 5-HIAA, the metabolic product of 5-HT, was not detected at all the samples selected. [ Conclusion] The L-Trp concentration of suckling piglets increase significantly with aging ( P 〈0. 05). While the concentra- tion of 5-HT and the conversion ratio of L-Trp to 5-HT are both highest at birth (P〈0.05) and keep stable at 5 and 15 d of age.
基金Effect of 5-hydroxytryptamine Receptor in the Lower Esophageal Sphincter Regulation Mechanism(Number:18ZF23)。
文摘In the first and second parts of this study,5-hydroxytryptamine(5HT)receptors,including 5-HT3 and 5-HT4 with the highest expression level,were found in clasp and sling fibres of the lower esophageal sphincter(LES).Specific 5-HT3 and 5-HT4 receptor agonists can induce the contraction effect of clasp and sling fibres of the LES while specific 5-HT7 receptor agonists showed no effects.In the study of this part,the in-vitro muscle tension measurement technology and EFS methods were used to detect the effect of the selective 5-HT receptor antagonist on the clasp and sling fibres of the in-vitro LES under the electrical field stimulation(EFS),and further to ensure the effect of 5-HT receptor in the LES neuroregulatory pathway,and deeply explore the effect of 5-HT receptor in the systolic and diastolic function regulation of the LES.
文摘We evaluated the genotypes of the serotonin transporter gene (5-HTT) in patients with premature ejaculation (PE) to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the patient subgroups. A total of 70 PE patients and 70 controls were included in this study. All men were heterosexual, had no other disorders and were either married or in a stable relationship. PE was defined as ejaculation that occurred within 1 min of vaginal intromission. Genomic DNA from patients and controls was analyzed using polymerase chain reaction, and allelic variations of the promoter region of the serotonin transporter gene (5-HTTLPR) were determined. The 5-HTTLPR (serotonin transporter promoter gene) genotypes in PE patients vs. controls were distributed as follows: L/L 16% vs. 17%, L/S 30% vs. 53% and S/S 54% vs. 28%. We examined the haplotype analysis for three polymorphisms of the 5-HTTLPR gene: LL, LS and SS. The appropriateness of the allele frequencies in the 5-HTTLPR gene was analyzed by the Hardy-Weinberg equilibrium using the Z-test. The short (S) allele of the 5-HTTLPR gene was significantly more frequent in PE patients than in controls (P 〈 0.05). We suggest that the 5-HTTLPR gene plays a role in the pathophysiology of all primary PE cases. Further studies are needed to evaluate the relationship between 5-HTTLPR gene polymorphism and patient subgroup (such as primary and secondary PE) responses to selective serotonin reuptake inhibitors as well as ethnic differences.
基金supported by the National Natural Science Foundation of China(Nos.82071516,32171065,91949105,and 81771227)the Innovation Capability Support Program of Shannxi Province in China(No.2020TD-037)the Fundamental Research Funds for the Central Universities(Nos.GK202105001,GK202205019,and CK202205022),China.
文摘5-Hydroxytryptamine(5-HT)type 3 receptor(5-HT_(3)R)is the only type of ligand-gated ion channel in the 5-HT receptor family.Through the high permeability of Na+,K+,and Ca2+and activation of subsequent voltage-gated calcium channels(VGCCs),5-HT_(3)R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system(CNS).5-HT_(3)Rs are widely expressed in the medial prefrontal cortex(mPFC),amygdala(AMYG),hippocampus(HIP),periaqueductal gray(PAG),and other brain regions closely associated with anxiety reactions.They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions.5-HT_(3)Rs mediate the activation of the cholecystokinin(CCK)system in the AMYG,and theγ-aminobutyric acid(GABA)“disinhibition”mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons(IINs).In contrast,a 5-HT_(3)R-induced GABA“disinhibition”mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects.5-HT_(2)R-mediated regulation of anxiety reactions are also activated by 5-HT_(3)R-activated 5-HT release in the HIP and PAG.This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT_(3)Rs.However,given the circuit specific modulation of 5-HT_(3)Rs on emotion,systemic use of 5-HT_(3)R agonism or antagonism alone seems unlikely to remedy anxiety,which deeply hinders the current clinical application of 5-HT_(3)R drugs.Therefore,the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.
基金the Natural Science Foundation of Chongqing City, No. CSTC2006BB5037
文摘BACKGROUND:Motoneurons from the Onuf’s nucleus of the spinal cord, which innervate the striated muscle of the pelvic floor, play an important role in erection, ejaculation, and urine control. Serotonin (5-hydroxytryptamine, 5-HT) regulates motoneuron activity from the Onuf’s nucleus of the spinal cord. However, few studies exist that describe 5-HT receptor distribution in the Onuf’s nucleus. In addition, the nature of the effects of 5-HT receptor on the innervating striated muscle of the pelvic floor is controversial. OBJECTIVE: To investigate the distribution of serotonin 5-HT2A and 5-HT7 receptors in motoneurons of Onuf’s nucleus in the spinal cord of male rats, and to analyze the relationship of 5-HT2A and 5-HT7 receptor to central modulation of urogenital function. DESIGN, TIME AND SETTING: The neural morphology experiment was performed at the Ultramicro-structure Laboratory of Reproductive Medicine, Basic Medical College, Chongqing Medical University, China from April to December 2007. MATERIALS: Ten adult, Sprague Dawley rats (eight males and two females) were randomly divided into gender control group (n = 4, 50% male and 50% female) and a retrograde tracing group (n = 6, 100% male) Recombinant pseudorabies virus (PRV-152) was provided by Professor LW Enquist from Princeton University, USA. Rabbit anti-5-HT2A and 5-HT7 receptor antibodies were purchased from Diasorin, France. METHODS: In the gender control group, the spinal L5-6 segments were harvested, sliced, and then incubate antibodies specific against 5-HT2A or 5-HT7 receptors for immunohistochemical staining. In the retrograde tracing group, PRV-152 was separately injected into the right ischiocavernosus (ischiocavernosus subgroup, n = 3) and the right external urethral sphincter (external urethral sphincter subgroup, n = 3). Four days after injection, L5-6 segments were harvested, sliced, and incubated with antibodies specific against 5-HT2A or 5-HT7 receptors for double-labeling immunofluorescence staining. MAIN OUTCOME MEASURES: Distribution analysis of 5-HT2A and 5-HT7 receptors in Onuf’s nucleus utilizing optical or laser confocal microscopy. RESULTS: 5-HT2A receptor immunoreactivity was revealed primarily in the medial region of the dorsolateral nucleus of Onuf’s nucleus. 5-HT7 receptor expression was observed in the lateral part of the dorso-lateral nucleus. 5-HT2A and 5-HT7 receptor expressions in the Onuf’s nucleus were significantly greater in male rats, compared to female rats. Double-labeling immunofluorescence demonstrated that 5-HT2A recepto were distributed primarily in the surrounding motoneurons innervating the ischiocavernosus, and 5-HT7 receptors were primarily expressed in motoneurons innervating the external urethral sphincter. CONCLUSION: Motoneurons innervating the ischiocavernosus and external urethral sphincter are located primarily in the medial and lateral region of the dorsolateral nucleus of L5-6 segments. The 5-HT2A receptor-innervating ischiocavernosus may be preferentially involved in the regulation of sexual reflex, and the 5-HT7 receptor-innervating external urethral sphincter may mainly join in regulating micturition reflex.
文摘<b><span style="font-family:Verdana;">Background:</span></b><span style="font-family:""><span style="font-family:Verdana;"> It is not well analyzed whether there are differences in plasma levels of tryptophan (TRP) metabolites between healthy control people (HC) and patients of major monopolar depression (MMD). </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> Ultra high-speed </span></span><span style="font-family:""><span style="font-family:Verdana;">liquid chromatography/mass spectrometry has been used for the simultaneous determination of plasma levels of tryptophan metabolites in depressive </span><span><span style="font-family:Verdana;">patients. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> There are no significant differences between plasma levels of TRP between HC and MMD. Plasma levels of TRP of HC are higher in young men, young women, old men, and old women in this order. Serotonin (5-HT) levels are higher in MMD than HC. Plasma levels of 5-HIAA of HC are also higher than those of patients of MMD. Plasma levels of kynurenine (KYN) of healthy old men and old women are higher than those of young men and old women. Plasma levels of KYN are higher in old women and young men of MMD than those of HC. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> Plasma levels of 5-HT are higher in patients of MMD than those of HC, which may suggest that use of drugs inhibiting the 5-HT transportation may increase plasma levels of 5-HT in MMD.
文摘目的评价单独使用磷酸二酯酶-5型(PDE5)抑制剂或联合五羟色胺再摄取抑制剂(SSRIs)对比单独应用SSRIs治疗勃起功能障碍(ED)与早泄(PE)共病的疗效与安全性。方法检索下述网站:知网、PubMed、Web of Science、Embase、万方、维普数据库、中国生物医学文献服务系统、中华医学期刊,自建库起至2022年11月,单独使用PDE5抑制剂或联合SSRIs对比单独应用SSRIs治疗ED与PE共病的随机对照试验,用Revman 5.4.1软件分析阴道内射精潜伏期(IELT)、国际勃起功能指数5项问卷(IIEF-5)评分及不良反应率。结果最终纳入文献9篇,涉及793例患者。Meta分析显示:与单独应用SSRIs治疗ED与PE共病相比,单独使用PDE5抑制剂或联合SSRIs治疗后患者IELT更高[MD=1.99,95%CI(1.51~2.46),P<0.001]、IIEF-5评分更高[MD=4.61,95%CI(3.68~5.55),P<0.001],不良反应无统计学差异[RR=0.99,95%CI(0.74~1.31),P=0.92]。结论治疗ED与PE共病患者时,应优先治疗ED或同时治疗ED和PE,在ED和PE方面都能获得更好的治疗效果,同时不良反应也没有增加。
文摘Serotonin is one of the significant signaling molecules used by several neural systems in the gut and brain. This study aimed to develop a novel and potent tracer for targeting, detecting, and imaging serotonin receptors(5-HTRs), which is a promising tool in the determination of the receptor’s function and relationship with the diseases related to serotonin and its receptor dysfunction. Serotonin was effectively labeled via a direct electrophilic substitutional reaction using an oxidizing agent such as iodogen with 125I in a neutral medium, and 125I-serotonin was achieved with a maximum labeling yield of 91 ± 0.63% with in vitro stability up to 24 h. Molecular modeling was conducted to signify 125I-serotonin structure and confirm that the radiolabeling process did not affect serotonin binding ability to its receptors. Biodistribution studies show that the maximum gastro intestinal tract uptake of 125I-serotonin was 17.8 ± 0.93% ID/organ after 30 min postinjection and the tracer’s ability to pass the blood–brain barrier. Thus, 125I-serotonin is a promising single photon emission computed tomography tracer in the detection of 5 HTRs.
文摘The present study examines the effects of serotonin (5-HT) 1A receptor ligands on humoral im-mune response in two rat lines selected for over 75 generations for the enhancement or elimination of aggression. Activation of presynaptic 5-HT1A receptors with a low dose of the selective 5-HT1A receptor agonist 8-OH-DPAT (0.1 mg/kg) or the blockade of postsynaptic 5-HT1A receptors with the antagonist WAY-100635 (1.0 mg/kg) did not affect the numbers of IgM-antibody forming cells (IgM-AFC) in the spleen of highly aggressive rats, which were characterized by higher immune responsiveness compared to nonaggressive line. On the other hand, the same doses of 8-OH-DPAT and WAY-100635, as well as a higher dose of 8-OH-DPAT (1.0 mg/kg), which is known to activate postsynaptic 5-HT1A receptors, produce immunostimulation in nonaggressive rats. However, only the highest dose of 8-OH-DPAT (5.0 mg/kg) was able to cause immunosuppression in nonaggressive rats that was mainly dependent on stimulation of postsynaptic 5-HT1A receptors. In contrast to nonaggressive rats, the dose of 1.0 mg/kg 8-OH-DPAT was sufficient to produce a decrease in the numbers of IgM-AFC in highly aggressive rats. Thus, pharmacological activation of pre- and postsynaptic 5-HT1A receptors, as well as the blockade of postsynaptic 5-HT1A receptors, produced different effects on the immune response in two lines of rats selected for high level of aggression or its absence. These data may have implications for more efficient treatments of a number of mental disorders associated with abnormal aggression.
文摘In our report, the values of whole blood serotonin (5-HT) in 87 apudoma patients (diagnosed by operation and pathology) were summarized. Among them, the levels of urinary 5-hydroxyindole-3-acetic acid (5-HIAA) of 44 patients were also tested. The results showed that both parametres of apudoma patients were higher than those of non-apudoma, post-operative patients of apudoma as well as the normal. The increasing extent of the levels of whole blood 5-HT and urinary 5-HIAA in small intestinal carcihoid was the most obvious one but that of rectum was not. The referable diagnostic values suggested were: 5-HT>130 ng ml, 5-HIAA>30 mg/ 24 hours.