Plasma Serotonin Concentrations Research Articles

TSPAN5 influences serotonin and kynurenine: pharmacogenomic mechanisms related to alcohol use disorder and acamprosate treatment response

We previously reported that SNPs near TSPAN5 were associated with plasma serotonin (5-HT) concentrations which were themselves associated with selective serotonin reuptake inhibitor treatment outcomes in patients with major depressive disorder (MDD). TSPAN5 SNPs were also associated with alcohol consumption and alcohol use disorder (AUD) risk. The present study was designed to explore the biological function of TSPAN5 with a focus on 5-HT and kynurenine concentrations in the tryptophan pathway. Ethanol treatment resulted in decreased 5-HT concentrations in human induced pluripotent stem cell (iPSC)-derived neuron culture media, and the downregulation of gene expression of TSPAN5, DDC, MAOA, MAOB, TPH1, and TPH2 in those cells. Strikingly, similar observations were made when the cells were treated with acamprosate—an FDA approved drug for AUD therapy. These results were replicated in iPSC-derived astrocytes. Furthermore, TSPAN5 interacted physically with proteins related to clathrin and other vesicle-related proteins, raising the possibility that TSPAN5 might play a role in vesicular function in addition to regulating expression of genes associated with 5-HT biosynthesis and metabolism. Downregulation of TSPAN5 expression by ethanol or acamprosate treatment was also associated with decreased concentrations of kynurenine, a major metabolite of tryptophan that plays a role in neuroinflammation. Knockdown of TSPAN5 also influenced the expression of genes associated with interferon signaling pathways. Finally, we determined that TSPAN5 SNPs were associated with acamprosate treatment outcomes in AUD patients. In conclusion, TSPAN5 can modulate the concentrations of 5-HT and kynurenine. Our data also highlight a potentially novel pharmacogenomic mechanism related to response to acamprosate.

Unreliability of EDTA samples for measuring bioamine neurotransmitter levels in cats.

The aim of this study was to assess the reliability of an EDTA-based method for measuring cat blood bioamines. Test 1 involved collecting blood samples from seven university laboratory cats. The samples were transferred to EDTA, heparin and plain tubes to determine concentrations of four bioamines (serotonin, dopamine, epinephrine [adrenaline] and norepinephrine [noradrenaline]). Correlation of measurements performed on EDTA plasma, with those performed on heparinized plasma or serum were assessed by intraclass correlation coefficients (ICCs). In test 2, blood samples from five owned cats were collected and stored in EDTA tubes and divided between duplicate Eppendorf tubes labeled as different cats for blinding purposes and analyzed independently for the same four bioamines as in test 1. Reliability of concentration determination for these duplicates was assessed by ICCs and coefficients of variation (CVs). In test 1, there was no significant correlation between the EDTA plasma serotonin and serum serotonin concentrations. There was also no significant correlation between EDTA plasma and heparin plasma concentrations for either epinephrine or norepinephrine. There was a statistically significant but weak correlation between EDTA plasma and heparin plasma dopamine concentrations. In test 2, there was no correlation for repeat-analyzed serotonin and epinephrine concentrations. Although there were statistically significant correlations for dopamine and norepinephrine, CVs for each analyte were in excess of 30%. Before any further attempt is made to measure and report on neurotransmitter concentrations in domestic cats, it is essential that the robustness of the methodology is carefully validated and the data presented.

The Combination of Dietary Branched-Chain and Limiting Amino Acids Modulates Feed Intake Through Both Peripheral and Central Mechanisms in Pigs Fed with Low Protein Diets

Abstract Objectives Due to its negative influence on human health and environment, excess nitrogen excretion is challenging the sustainability of swine industry. Severe reduction of dietary protein may reduce the excretion of nitrogen from swine production, but this results in poor growth performance of pigs. The aim of current study was to investigate the effect of supplementing LP diets with both branched-chain amino acids (BCAA; i.e., leucine, isoleucine, valine) and other limiting amino acids (LAA; i.e., lysine, methionine, threonine, tryptophan) at levels higher than suggested requirements on the growth performance and mRNA and protein abundance of markers associated with feed intake in nursery pigs. Methods Forty-eight weaned barrows at 3 weeks of age were individually housed and following 2 weeks of adaptation, randomly assigned to 6 treatments for 4 weeks: 1) positive control: 20% crude protein (CP); 2) negative control (NC): 14% CP; 3) NC + LAA 25% more than suggested levels (L25); 4) NC + LAA 50% more than suggested levels (L50); 5) NC + LAA and BCAA 25% more than suggested levels (LB25); 6) NC + LAA and BCAA 50% more than suggested levels (LB50). At week 4 of starting experimental diets, all pigs were euthanized and blood samples, hypothalamus and jejunum samples collected. The data were analyzed with univariate GLM (SPSS®). Results Final body weight was significantly higher in LB50 than L50. The pigs fed with LB50 and LB25 had higher average daily feed intake than L50 and L25, respectively. The LB50 reduced the plasma serotonin concentration relative to L50 and NC. The overall effect of diet on mRNA abundance of hypothalamic tryptophan hydroxylase 1 (TPH1) and 5-hydroxytryptamine receptor 2B (5HTR2B) was significant, but no differences among groups were detected. The pigs in LB50 and LB25 had higher mRNA abundance of hypothalamic NPY (∼20%) than NC. Conclusions Supplementing the LP diets with increased levels of both dietary BCAA and LAA reduced the plasma serotonin concentration and improved the growth performance and feed intake partly through increased hypothalamic NPY. Funding Sources This work was supported by Animal Health and Production and Animal Products: Improved Nutritional Performance, Growth, and Lactation of Animals and by Hatch project from the USDA National Institute of Food and Agriculture.

Influence of toys on behavioural patterns of pigs and their association with the concentration of serotonin in blood plasma

Improvement of welfare of piglets is one of the key factors which underlie the effectiveness of producing pork and the profitability of pig farming. This article offers a solution to the main industrial problem – creation of comfortable maintenance conditions for pigs using toys which satisfy their ethological needs. Piglets used in the experiment were kept in the swine complex of agricultural production of Agrofirm Mig-Service-Agro Cooperative in Novoodesky district of Mykolaiv Oblast (Ukraine). The objective of the study was assessment of the effect of toys on the behaviour of piglets, level of concentration of hormone serotonin in blood plasma and their energy of growth. The experiment was performed on 120 weaned piglets aged 28 days, which were divided according to the principle of analogues with 60 individuals in each group: I – the control group, the animals were kept with no toys; II – the experimental group, where the animals had toys. During the experiment chronometric monitoring of the piglets’ behavioural acts was carried out using video observation, we extracted blood samples for determination of the content of the hormone serotonin using the method of highly-efficient fluid chromatography and assessed the growth of the piglets. After the end of the experiment, we determined that the presence of toys reduced the intragroup aggression, which was accompanied by decrease in the duration of fights and almost three-fold increase in playing behaviour. Among piglets which had access to toys, the number of individuals observed to bite tails and ears decreased from 11 to 3. In the period of the study, the concentration of serotonin in the blood plasma of piglets who had free access to toys was 10 times higher compared with animals of the control group. Change in the behaviour patterns among the animals of the experimental group led to significant differences regarding the parameters of growth, where probable increase in the live weight at the age of 90 days was observed, which was associated with significant increase in their mean daily weight gain compared with the animals of the control group. This study confirms that use of toys for piglets during growth completion can prevent features of aggression and abnormal forms of stereopathy within groups, increase the live weight and mean daily weight gain and improve emotional condition, which affects the welfare of pigs.

Monoamine oxidase polymorphisms in rhesus and Japanese macaques (Macaca mulatta and M. fuscata)

Monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) are enzymes that degrade several monoamines of the central nervous system and have long been implicated in the modulation of social behavior. Macaque monkeys are a suitable model for investigating the role of functional monoamine oxidase polymorphisms in behavior modulation given the high amount of social diversity among the nearly two dozen species. The present study reports allele frequencies for two polymorphisms, MAOA-LPR and MBin2, in samples of rhesus (Macaca mulatta) and Japanese (M. fuscata) macaques. Our results suggest that the two species may differ in high- and low-activity MAOA-LPR allele frequencies. Specifically, 89% of the Japanese macaque alleles in our sample were the low-activity variant, whereas only 41% of the rhesus macaque alleles were of this sort. In our samples, the two species possessed similar allelic variation at the MBin2 locus, with each possessing some species-specific alleles. We also tested for associations between MAOA-LPR genotype and plasma serotonin (5-HT) and dopamine (DA) concentrations in a subset of rhesus macaques, which revealed no association with genotype. Our findings point toward potential differences in the monoaminergic system of two closely related macaque species. Discussion of our results are centered on implications for future investigations that aim to better understand the functionality of monoamine oxidase polymorphisms in the context of primate social behavior.

Wheat Protein Hydrolysate Fortified With l-Arginine Enhances Satiation Induced by the Capsaicinoid Nonivamide in Moderately Overweight Male Subjects.

ScopeIncreasing the intake of satiety‐enhancing food compounds represents a promising strategy for maintaining a healthy body weight. Recently, satiating effects for the capsaicinoid nonivamide have been demonstrated. As various proteins and amino acids have also been demonstrated to decrease energy intake, oral glucose tolerance test (oGTT)‐based bolus interventions of 75 g glucose + 0.15 mg nonivamide (NV control) are tested with/without combination of a wheat protein hydrolysate (WPH: 2 g) and/or l‐arginine (ARG: 3.2 g) for their satiating effects in 27 moderately overweight male subjects.Methods and ResultsCompared to NV control intervention, ARG and WPH + ARG treatment both reduce (p < 0.01) total calorie intake from a standardized breakfast by –5.9 ± 4.15% and –6.07 ± 4.38%, respectively. For the WPH + ARG intervention, increased mean plasma serotonin concentrations (AUC: 350 ± 218), quantitated by ELISA, and delayed gastric emptying, assessed by 13C‐Na‐acetate breath test (−2.10 ± 0.51%, p < 0.05), are demonstrated compared to NV control. Correlation analysis between plasma serotonin and gastric emptying reveals a significant association after WPH ± ARG intervention (r = –0.396, p = 0.045).ConclusionCombination of WPH and ARG enhances the satiating effect of nonivamide, providing opportunities to optimize satiating food formulations by low amounts of the individual food constituents.

Urine 5-hydroxyindoleacetic acid in Cavalier King Charles spaniels with preclinical myxomatous mitral valve disease

Higher concentrations of circulating serotonin have been reported in Cavalier King Charles spaniels (CKCS) compared to other dog breeds. The CKCS is also a breed highly predisposed to myxomatous mitral valve disease (MMVD). The aim of this study was to determine urine concentrations of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite and excretion product of serotonin, in a population of CKCS with preclinical MMVD, and to evaluate whether urine 5-HIAA concentrations were associated with MMVD severity, dog characteristics, setting for urine sampling, platelet count, and serotonin concentration in serum and platelet-poor plasma (PPP). The study population consisted of 40 privately-owned CKCS (23 females; 17 males) with and without preclinical MMVD as follows: American College of Veterinary Internal Medicine (ACVIM) group A (n = 11), ACVIM group B1 (n = 21) and ACVIM group B2 (n = 8).Urine 5-HIAA concentrations were not significantly associated with preclinical MMVD disease, platelet count or circulating concentrations of serotonin (in serum and PPP; P > 0.05). Females had higher 5-HIAA concentrations than males in morning urine collected at home (females, 3.1 [2.9–3.7] μmol/mmol creatinine [median and quartiles]; males, 1.7 [1.2–2.2] μmol/mmol creatinine; P = 0.0002) and urine collected at the clinic (females, 3.5 [3.1–3.9] μmol/mmol creatinine; males, 1.6 [1.3–2.1] μmol/mmol creatinine; P < 0.0001). Five-HIAA concentrations in urine collected at home and at the clinic were significantly associated (P = 0.0004; r = 0.73), and higher concentrations were found in urine collected at the clinic (P = 0.013). Urine 5-HIAA concentration was influenced by sex and setting of urine sampling. Urine 5-HIAA concentration was not associated with MMVD severity or circulating concentrations of serotonin in CKCS with preclinical disease.

Decreased plasma serotonin and other metabolite changes in healthy adults after consumption of wholegrain rye: an untargeted metabolomics study

Wholegrain consumption has been associated with beneficial health effects including reduction of diabetes and cancer risk; however, the underlying mechanisms are not fully understood. The aim of this study was to characterize the effects of wholegrain rye intake on circulating metabolites in a human intervention study using untargeted metabolomics. The intervention consisted of 2 successive 4-wk periods in a randomized crossover design, where 15 adults consumed wholegrain rye bread (WGR) or white wheat bread enriched with fermented rye bran (WW+RB), following a 4-wk rye-free period with white wheat bread (WW). Fasting plasma samples were collected at the end of each period and analyzed using liquid chromatography-mass spectrometry. Metabolic profiles were compared to identify compounds discriminating WGR from the WW+RB and WW periods. Because peripheral serotonin is produced mainly in the gut, a hypothesis of its altered biosynthesis as a response to increased cereal fiber intake was tested by measuring intestinal serotonin of mice fed for 9 wk on a high-fat diet supplemented with different sources of fiber (rye bran flour, ground wheat aleurone, or powdered cellulose). Five endogenous metabolites and 15 rye phytochemicals associated with WGR intake were identified. Plasma concentrations of serotonin, taurine, and glycerophosphocholine were significantly lower after the WGR than WW period (Q<0.05). Concentrations of 2 phosphatidylethanolamine plasmalogens, PE(18:2/P-18:0) and PE(18:2/P-16:0), were lower after the WGR period than the WW+RB period (Q<0.05). The concentration of serotonin was significantly lower in the colonic tissue of mice that consumed rye bran or wheat aleurone compared with cellulose (P<0.001). Wholegrain rye intake decreases plasma serotonin in healthy adults when compared with refined wheat. Intake of rye bran and wheat aleurone decreases colonic serotonin in mice. These results suggest that peripheral serotonin could be a potential link between wholegrain consumption and its associated health effects.Data used in the study were derived from a trial registered at www.clinicaltrials.gov as NCT03550365.

Dietary Supplementation with Lysine and Threonine Modulates the Performance and Plasma Metabolites of Broiler Chicken.

Here, we investigated whether the optimal threonine (Thr) to lysine (Lys) ratio in high Lys diet improves the growth performance of modern broiler chickens at finisher period and determined the possible mechanism underlying improvement in the growth performance of chickens fed with high Lys or Lys + Thr diet using metabolome analyses. Eighteen 21-day-old chickens housed in individual cages were randomly divided into three groups of six chickens fed with different diets as follows: control diet, high Lys diet (150% Lys content of National Research Council requirement), and high Lys + Thr diet (0.68 of Thr/Lys in high Lys diet). Body weight gain (BWG) increased in chickens receiving high Lys diet as compared with those fed with the control diet (P<0.05); no significant difference was observed in BWG of chickens from high Lys + Thr and high Lys groups. Feed conversion ratio (FCR) was lower in chickens fed with high Lys or high Lys + Thr diet than in those on the control diet. Serotonin concentration increased in the plasma of chickens fed with high Lys diet as compared to those fed with other diets. A negative correlation was observed between plasma serotonin concentration and FCR. These results provide the first evidence on the use of high Lys in broiler diets to reduce FCR during finisher period, which may be associated with change in plasma serotonin concentration. These findings suggest that high Lys content in finisher diet, but not high Thr + Lys diet, may affect the peripheral serotonergic metabolism and improve FCR. Thus, plasma serotonin may serve as a biomarker of FCR in broilers.

The effect of Toxoplasma gondii on plasma serotonin concentration in sheep.

Background and Aim:Toxoplasma gondii is an intracellular parasite that commonly infects warm-blooded animals, including humans. Virtually all species can be infected, but a species-specific variability is evident, in terms of both type and severity of the symptoms encountered. As serotonin (5-hydroxytryptamine [5-HT]) plays an important regulatory role in both physiological and immune responses, the aim of this research was to assess whether toxoplasmosis disease could affect plasma 5-HT concentration and/or hematochemical parameters in a particularly susceptible species to infection as sheep.Materials and Methods:5-HT plasma levels were analyzed in platelet-poor plasma fraction by enzyme-linked immunosorbent assay. Blood count and hematochemical parameters were evaluated. Total proteins (TPs), glucose (Glu), and lactate dehydrogenase were determined by a spectrophotometer.Results:Results showed significantly higher levels in plasma 5-HT, monocytes, and TP and significantly lower levels of Glu, in infected sheep compared to the control group.Conclusion:Results could support the hypothesis of an effect of toxoplasmosis infection on plasma 5-HT concentrations in sheep. More research is needed to assess the function of 5-HT in the regulation of infected sheep’s immune responses.

Effect of preemptive dezocine before general anesthesia on postoperative analgesia in patients undergoing laparoscopic cholecystectomy: A prospective observational study.

Dezocine is proposed as an adjunctive analgesic for postoperative pain control. This randomized, double-blind, controlled study aimed to investigate the effect of preoperative Dezocine therapy on postoperative pain following laparoscopic cholecystectomy as well as the underlying mechanisms.Eighty patients scheduled for laparoscopic cholecystectomy were randomly allocated into 2 groups as follows: patients in Group D received Dezocine 0.15 mg/kg before anesthesia induction and patients in Group S received same volume of saline. The pain intensity, sedation score, sufentanil-based patient-controlled analgesia (PCA) consumption were recorded for 24 hours after surgery. Plasma concentrations of norepinephrine and serotonin were also measured.During the first 24 hours after surgery, the patients in Group D experienced lower pain score assessed by numerical rating scale (NRS) at 3 hours (rest: P = .038; movement: P = .036), 6 hours (rest: P = .038; movement: P = .036), 12 hours (rest: P = .038; movement: P = .036), and 24 hours (rest: P = .038; movement: P = .036). Dezocine also decreased the sedation levels at 5 minutes (P = .031) after arrival at the PACU. Sufentanil-based PCA consumption in Group D was decreased when compared with Group S in the second to fourth phase after surgery (6–12 hours: P = .017; 12–18 hours: P = .003; 18–24 hours: P = .039). Plasma norepinephrine and serotonin concentrations were higher in the Group D at 24 hours after surgery (norepinephrine: P = .009, serotonin: P = .042). In addition, Group D showed less incidence of nausea/vomiting (P = .032) as well as a higher postoperative satisfaction score after surgery (P = .017).In conclusion, preemptive Dezocine administration is suggested to be useful for the management of postoperative pain in short-lasting surgery such as laparoscopic cholecystectomy.

Does fluoxetine exposure affect hypoxia tolerance in the Gulf toadfish, Opsanus beta?

Due to ineffective wastewater treatment technologies, pharmaceuticals such as the selective serotonin reuptake inhibitors (SSRIs)—a common class of antidepressants which inhibit the serotonin transporter (SERT)—can be found in surface waters and marine receiving waters near wastewater effluents. Understanding how exposure to these chemicals might impact non-target organisms, especially combined with other environmental stressors like hypoxia, is essential in order to thoroughly evaluate environmental risk. It was hypothesized that both acute and chronic exposure to the SSRI fluoxetine (FLX) would interfere with the metabolic hypoxia response of the Gulf toadfish, Opsanus beta. Here we demonstrate that acute intraperitoneal treatment with 50 μg g−1 FLX significantly reduces the regulation index, or degree of metabolic regulation, in toadfish. Acute FLX exposure significantly reduced SERT mRNA expression in the first and third gill arches, but mRNA expression was not affected in heart tissues or in the second gill arch. In contrast, the regulation index was unaffected by 14–17 day waterborne FLX exposure to environmentally relevant (0.01 μg L−1) and approximately 1000-fold higher (8.5 μg L−1) concentrations. However, the higher concentration was sufficient to induce a systemic elevation in plasma serotonin concentrations. Chronic FLX exposure did not alter SERT mRNA expression in heart or gill tissues. The results of this study implicate the involvement of 5-HT pathways in hypoxia tolerance but demonstrate that current environmental levels of FLX are insufficient to impair the metabolic hypoxia response in marine fish.

Effect of transcutaneous electrical acupoint stimulation on postoperative analgesia after ureteroscopic lithotripsy: a randomized controlled trial.

Transcutaneous electrical acupoint stimulation (TEAS) is an effective analgesic measure. We studied the analgesic effect of TEAS by applying it alone after ureteroscopic lithotripsy, rather than applying it as a supplementary analgesic measure. Participants (n = 120) scheduled to undergo ureteroscopic holmium laser lithotripsy, were enrolled and randomly assigned into Group T (TEAS n = 60) and Group C (Control, n = 60). The participants in Group T were treated with TEAS for postoperative analgesia. TEAS were implemented on bilateral Shenyu (BL23) and Yinlingquan (SP9) at the time backward and the time at 4, 8, 12h postoperatively. TEAS was re-implemented three times on the target acupoints for the next 2days. When TEAS failed to meet the analgesic effect, the participants were given tramadol hydrochloride tablets of 100mg. Participants of Group C were given tramadol hydrochloride tablets for postoperative analgesia. The primary outcome of VAS scores at the time backward (T0), 4h (T1), 12h (T2), 24h (T3), 48h (T4) postoperatively and the amount of remedy for analgesic consumption within 48h postoperatively were compared. The secondary outcome of adverse reactions and plasma concentrations of serotonin (5-HT) and substance P (SP) at T0, T1, T2, T3, T4 were detected, respectively. The VAS scores at T1, T2, T3, T4 postoperatively in two groups were lower than T0. Compared to group C, the VAS scores at T1 (3.68 ± 0.68 vs. 4.79 ± 0.82, P = 0.01), T2 (2.64 ± 0.72 vs. 3.92 ± 0.88, P = 0.03), T3 (2.21 ± 0.88 vs. 3.38 ± 0.74, P < 0.01) in Group T were lower, and total remedy of analgesic consumption was significantly lower (127.14 ± 28.46 vs. 415.27 ± 86.37, P < 0.01) within 48h postoperatively. The plasma concentrations of 5-HT in Group T was lower than Group C at T1 (348.54 ± 138.49 vs. 418.69 ± 124.68, P = 0.03), T2 (324.28 ± 112.73 vs. 398.52 ± 114.53, P < 0.01), T4 (309.64 ± 129.09 vs. 388.46 ± 115.36, P = 0.04) postoperatively and concentrations of SP at T1 (59.38 ± 24.68 vs. 78.93 ± 26.32, P < 0.01), T2 (49.36 ± 25.55 vs. 66.49 ± 23.57, P = 0.02), T3 (42.19 ± 24.36 vs. 64.15 ± 28.16, P = 0.04), T4 (39.26 ± 19.88 vs. 54.64 ± 20.62, P = 0.02) postoperatively were also lower than Group C. Meanwhile, the occurrences of vertigo (6.7 vs. 18.3%, P < 0.01), nausea and vomiting (11.7 vs. 21.7%, P < 0.01), constipation (10.0 vs. 20.0%, P = 0.03) in Group T were also lower. Application of TEAS alone was associated with effective alleviation of postoperative pain, reduction of postoperative analgesics consumption, decrease of plasma concentration of algogenic substance and the incidence of adverse reactions after ureteroscopic lithotripsy.

SSRI-reduced platelet reactivity in non-responding patients with life-long Recurrent Depressive Disorder: Detection and involved mechanisms

IntroductionAdverse effects with bleeding disorders are often associated with the administration of SSRI in depression, although the exact mechanisms remain contradicting. This study is aimed at detecting and exploring the mechanisms of SSRI-induced changes in platelet reactivity in non-responding patients with Recurrent Depressive Disorder (RDD) and life-long exposure to antidepressants. Materials and methodsThirty-one patients and thirty-one healthy controls were included in the study. A comprehensive approach which includes evaluation of peripheral markers and microscopic analyses of platelet morphology changes has been used. ResultsRDD SSRI patients have shown blunted aggregatory responses towards collagen and epinephrine. Evident differences in the microscopic evaluation of platelet morphology were observed between the groups, with inherent absence of micro-aggregates and platelet shape changes within the patients; after quantification, the sensitivity and specificity of this method were assessed as high. The abnormalities were found in association with lower platelet serotonin content and high fluctuations of free plasma serotonin levels. Changes in the levels of CRP, fibrinogen and nitric oxide were not observed. Macroplatelets were also detected within RDD SSRI patients via increased MPV, PDW and P-LCR, which were associated with discoid shape and without procoagulant activity. ConclusionsThe microscopic evaluation might be useful as a simple method for detection of SSRI-reduced platelet function for research purposes or systematic correlations with other biochemical parameters. The mechanisms involved in SSRI-reduced platelet function in non-responding RDD patients are complex, including combined effects of lower platelet serotonin content, high fluctuations in plasma serotonin concentration and abnormal α-AR function.

Evaluation of peripheral serotonin content and α2-adrenergic receptor function as potential markers for life-long recurrent depressive disorder by using methodological improvements

Objective: We aimed to evaluate the role and the relations between peripheral platelet serotonin content, blood plasma serotonin concentration and the function of platelet α2-adrenergic receptors (α2-AR) as potential state or trait biomarkers for recurrent depressive disorder (RDD).Methods: 26 drug-free patients with life-long RDD and 31 healthy controls were included in the study. Several methodological improvements in blood collection and platelet isolation were implemented following the present standards in Haematology and Light transmission aggregometry.Results: Our results have shown lower platelet serotonin content, higher plasma serotonin concentration and desensitization of platelet α2-AR in patients with RDD. The variables were found heterogeneous and mainly influenced by the clinical characteristics of the current episode. High amplitude of the α2-AR correlated with severe anxious symptoms and high platelet serotonin content (as well as low plasma serotonin levels) were associated with psychotic symptoms.Conclusions: The evaluated peripheral markers reflect only state (but not trait) abnormalities in patients with current severe episode of RDD. The observed peripheral α2-AR and serotonin abnormalities are mutually not related and they are probably triggered by different mechanisms.

PCPA protects against monocrotaline-induced pulmonary arterial remodeling in rats: potential roles of connective tissue growth factor.

The purpose of this study was to investigate the mechanism of monocrotaline (MCT)-induced pulmonary artery hypertension (PAH) and determine whether 4-chloro-DL-phenylalanine (PCPA) could inhibit pulmonary arterial remodeling associated with connective tissue growth factor (CTGF) expression and downstream signal pathway. MCT was administered to forty Sprague Dawley rats to establish the PAH model. PCPA was administered at doses of 50 and 100 mg/kg once daily for 3 weeks via intraperitoneal injection. On day 22, the pulmonary arterial pressure (PAP), right ventricle hypertrophy index (RVI) and pulmonary artery morphology were assessed and the serotonin receptor-1B (SR-1B), CTGF, p-ERK/ERK were measured by western blot or immunohistochemistry. The concentration of serotonin in plasma was checked by ELISA. Apoptosis and apoptosis-related indexes were detected by TUNEL and western blot. In the MCT-induced PAH models, the PAP, RVI, pulmonary vascular remodeling, SR-1B index, CTGF index, anti-apoptotic factors bcl-xl and bcl-2, serotonin concentration in plasma were all increased and the pro-apoptotic factor caspase-3 was reduced. PCPA significantly ameliorated pulmonary arterial remodeling induced by MCT, and this action was associated with accelerated apoptosis and down-regulation of CTGF, SR-1B and p-ERK/ERK. The present study suggests that PCPA protects against the pathogenesis of PAH by suppressing remodeling and inducing apoptosis, which are likely associated with CTGF and downstream ERK signaling pathway in rats.

Reduced anxiety is associated with the accumulation of six serotonin reuptake inhibitors in wastewater treatment effluent exposed goldfish Carassius auratus

Pharmaceuticals and personal care products (PPCPs) have been found in wastewater treatment plant (WWTP) effluents and their recipient watersheds. To assess the potential of WWTP effluents to alter fish behaviour, we caged male goldfish (Carassius auratus) for 21-days at three sites along a contamination gradient downstream from a WWTP which discharges into Cootes Paradise Marsh, on the western tip of Lake Ontario. We also included a fourth caging site as an external reference site within Lake Ontario at the Jordan Harbour Conservation Area. We then measured concentrations of PPCPs and monoamine neurotransmitters in caged goldfish plasma, and conducted behavioural assays measuring activity, startle response, and feeding. We detected fifteen different PPCPs in goldfish plasma including six serotonin reuptake inhibitors (amitriptyline, citalopram, fluoxetine/norfluoxetine, sertraline, venlafaxine, and diphenhydramine). Plasma concentrations of serotonin were significantly greater in plasma of fish caged closer to the WWTP effluent outfall site. The fish caged near and downstream of the WWTP effluent were bolder, more exploratory, and more active overall than fish caged at the reference site. Taken together, our results suggest that fish downstream of WWTPs are accumulating PPCPs at levels sufficient to alter neurotransmitter concentrations and to also impair ecologically-relevant behaviours.

Appetite-Inducing Effects of Homoeriodictyol: Two Randomized, Cross-Over Interventions.

Anorexia of aging, characterized by a decrease in appetite and/or food intake, is a major risk factor of under-nutrition and adverse health outcomes in elderly people. Recent in vitro evidence suggests homoeriodictyol (HED), a naturally occurring, bitter-masking flavanone, as a promising agent to increase appetite and food intake. In two cross-over intervention trials, 30 mg NaHED, either solely (n=10, Study I) or in combination with a 75 g glucose load (n=17, study II) were administered to healthy adult subjects. Ratings of hunger were assessed at fasting and either 30 min (Study I) or 120 min (Study II) post intervention. Ad libitum energy intake from a standardized breakfast and plasma changes in hunger-/satiety-associated hormones PYY, GLP-1, ghrelin and serotonin were determined after blood drawings. Effects were more pronounced when NaHED was administered in combination with 75 g glucose since ad libitum energy (+9.52±4.60%) and protein (+7.08±7.97%) intake as well as plasma ΔAUC ghrelin values increased in study II solely, whereas plasma serotonin concentrations decreased after both interventions. NaHED demonstrated appetizing effects in healthy adults when administered with a glucose load. Long-term intervention studies are warranted to verify these effects in compromised subjects.

Gintonin attenuates depressive-like behaviors associated with alcohol withdrawal in mice

BackgroundPanax ginseng Meyer extracts have been used to improve mood and alleviate symptoms of depression. However, little is known about the extracts’ active ingredients and the molecular mechanisms underlying their reported anti-depressive effects. MethodsGintonin is an exogenous lysophosphatidic acid (LPA) receptor ligand isolated from P. ginseng. BON cells, an enterochromaffin cell line, and C57BL/6 mice were used to investigate whether gintonin stimulates serotonin release. Furthermore, the effects of gintonin on depressive-like behaviors following alcohol withdrawal were evaluated using the forced swim and tail suspension tests. ResultsTreatment of BON cells with gintonin induced a transient increase in the intracellular calcium concentration and serotonin release in a concentration- and time-dependent manner via the LPA receptor signaling pathway. Oral administration of the gintonin-enriched fraction (GEF) induced an increase in the plasma serotonin concentration in the mice. Oral administration of the GEF in mice with alcohol withdrawal decreased the immobility time in two depression-like behavioral tests and restored the alcohol withdrawal-induced serotonin decrease in plasma levels. LimitationsWe cannot exclude the possibility that the gintonin-mediated regulation of adrenal catecholamine release in the peripheral system, and acetylcholine and glutamate release in the central nervous system, could also contribute to the alleviation of depressive-like behaviors. ConclusionThe GEF-mediated attenuation of depressive-like behavior induced by alcohol withdrawal may be mediated by serotonin release from intestinal enterochromaffin cells. Therefore, the GEF might be responsible for the ginseng extract-induced alleviation of depression-related symptoms.

Exposing broiler eggs to green, red and white light during incubation

Previous work has shown that exposing broiler eggs to white light during incubation can improve hatchability and post-hatch animal welfare. It was hypothesized that due to how different wavelengths of light can affect avian physiology differently, and how pigmented eggshells filter light that different monochromatic wavelengths would have differential effects on hatchability and post-hatch animal welfare indicators. To determine, we incubated chicken eggs (n=6912) under either no light (dark), green light, red light or white light; the light level was 250 lux. White and red light were observed to increase hatch of fertile (P<0.05) over dark and green light incubated eggs. White, red and green light exposure during incubation improved (P<0.05) the proportion of non-defect chicks over dark incubated eggs. Post-hatch 45-day weight and feed conversion was not affected by light exposure of any wavelength (P>0.05). Fear response of during isolation and tonic immobility was reduced (P<0.05) in broilers incubated under white or red light when compared with either green or dark broilers. Broilers incubated with white or red light had lower (P<0.05) composite asymmetry scores and higher (P<0.05) humoral immunity titers than dark incubated broilers, however, green light broilers did not differ (P>0.05) from dark incubated broilers. All light incubated broilers had lower (P<0.05) plasma corticosterone and higher (P<0.05) plasma serotonin concentrations than dark incubated broilers. These results indicate that white light and red light that is a component of it are possibly the key spectrum to improving hatchability and lower fear and stress susceptibility, whereas green light is not as effective. Incubating broiler eggs under these spectrums could be used to improve hatchery efficiency and post-hatch animal welfare at the same time.