Plasma Serotonin Concentrations Research Articles

Platelet hyperresponsiveness and increased platelet-neutrophil aggregates in dogs with myxomatous mitral valve disease and pulmonary hypertension.

Pulmonary hypertension (PH) in dogs with myxomatous mitral valve disease (MMVD) is caused by increased pulmonary venous pressure. Thrombosis, vascular remodeling, and vasoconstriction mediated by platelets could exacerbate PH. Dogs with PH will exhibit a hypercoagulable state, characterized by increased platelet activation, platelet-leukocyte, and platelet-neutrophil aggregate formation. Eleven dogs (≥3.5 kg) diagnosed with MMVD and PH and 10 dogs with MMVD lacking PH. Prospective cohort ex vivo study. All dogs underwent echocardiographic examination, CBC, 3-view thoracic radiographs, and heartworm antigen testing. Severity of PH and MMVD were assessed by echocardiography. Viscoelastic monitoring of coagulation was assessed using thromboelastography (TEG). Platelet activation and platelet-leukocyte/platelet-neutrophil interactions were assessed using flow cytometry. Plasma serotonin concentrations were measured by ELISA. Unstimulated platelets from dogs with MMVD and PH expressed more surface P-selectin than MMVD controls (P = .03). Platelets from dogs with MMVD and PH had persistent activation in response to agonists. The number of platelet-leukocyte aggregates was higher in dogs with MMVD and PH compared with MMVD controls (P = .01). Ex vivo stimulation of whole blood resulted in higher numbers of platelet-neutrophil aggregates in dogs with MMVD and PH (P = .01). Assessment of hypercoagulability based on TEG or plasma serotonin concentrations did not differ between groups. Platelet hyperresponsiveness and increased platelet-neutrophil interaction occur in dogs with MMVD and PH, suggesting that platelets play a role of in the pathogenesis of PH. Clinical benefits of antiplatelet drugs in dogs with MMVD and PH require further investigation.

Short Road Transport and Slaughter Stress Affects the Expression Profile of Serotonin Receptors, Adrenocortical, and Hematochemical Responses in Horses.

Horse transport is considered a cause of stress in animals and is known to affect the 5-HT concentrations in both the brain and other tissues. The aim of this research was to investigate the effect of horse transportation and slaughter stress on plasma serotonin's concentration and the expression levels of the related 5-HT1B and 5-HT2A receptors in PBMCs. Furthermore, the IL-12 levels and a variety of blood parameters, including triglycerides, total cholesterol, glucose, aspartate aminotransferase, creatine phosphokinase, lactate dehydrogenase, were also considered. This research was carried out on 32 horses submitted to short road transport of 40 km to slaughter. Blood samples were collected in baseline conditions (T0) and 24 h later, after they were slaughtered (T1). The results showed a significantly increased expression of 5-HT1B and 5-HT2A receptors and a significantly decreased expression of IL-12 in PBMCs at T1 vs. T0. Furthermore, a significant increase in cortisol and glucose concentrations, and LDH activity was observed at T1. In contrast, a significantly lower circulating 5-HT concentration was observed at T1 vs. T0. These results indicate that the stress induced by transport and slaughter stimuli led to the serotoninergic system's activation, suggesting that the expression of serotonin receptors could be used as a pivotal marker of stress, with potential applications for the improvement of elective protocols to observe the guidelines relating to transported horses.

Duloxetine improves chronic orofacial pain and comorbid depressive symptoms in association with reduction of serotonin transporter protein through upregulation of ubiquitinated serotonin transporter protein.

Chronic orofacial pain (COP) is relieved by duloxetine (DLX) and frequently causes depressive symptoms. The aim of this study was to confirm effects of DLX on pain and depressive symptoms, and to associate with their effectiveness in platelet serotonin transporter (SERT) expression, which is a target molecule of DLX and plasma serotonin concentration in COP patients with depressive symptoms. We assessed for the severity of pain and depressive symptoms using the Visual Analog Scale (VAS) and 17-item Hamilton Depression Rating Scale (HDRS), respectively. Chronic orofacial pain patients were classified into 2 groups based on their HDRS before DLX-treatment: COP patients with (COP-D) and without (COP-ND) depressive symptoms. We found that the VAS and HDRS scores of both groups were significantly decreased after DLX treatment compared with those before DLX treatment. Upregulation of total SERT and downregulation of ubiquitinated SERT were observed before DLX treatment in both groups compared with healthy controls. After DLX treatment, there were no differences in total SERT of both groups and in ubiquitinated SERT of COP-D patients compared with healthy controls; whereas, ubiquitinated SERT of COP-ND patients remained downregulated. There were positive correlations between changes of serotonin concentrations and of VAS or HDRS scores in only COP-D patients. Our findings indicate that DLX improves not only pain but also comorbid depressive symptoms of COP-D patients. Duloxetine also reduces platelet SERT through upregulation of ubiquitinated SERT. As the result, decrease of plasma serotonin concentrations may be related to the efficacy of DLX in relieving pain and depression in COP patients.

Membrane Transporter of Serotonin and Hypercholesterolemia in Children.

The serotonin membrane transporter is one of the main mechanisms of plasma serotonin concentration regulation. Serotonin plays an important role in the pathogenesis of various cardiovascular diseases, stimulating the proliferation of smooth muscle cells, key cells in the process of hypertrophic vascular remodeling. Vascular remodeling is one of the leading prognostically unfavorable factors of atherosclerosis, the main manifestation of familial hypercholesterolemia. Familial hypercholesterolemia is one of the most common genetically determined lipid metabolism disorders and occurs in 1 in 313 people. The aim of our study was to investigate the levels of plasma and platelet serotonin, 5-hydroxyindoleacetic acid, and membrane transporter in a cross-sectional study of two pediatric groups, including patients with familial hypercholesterolemia and the control group, which consisted of apparently healthy children without cardiovascular diseases. The study involved 116 children aged 5 to 17 years old. The proportion of boys was 50% (58/116) and the average age of the children was 10.5 years (CI 2.8-18.1). The concentrations of serotonin in blood plasma and platelets and 5-hydroxyindoleacetic acid were higher in children with familial hypercholesterolemia than in the controls. The concentration of the serotonin transporter in platelets in healthy children, compared with the main group, was 1.3 times higher. A positive correlation was revealed between the level of serotonin (5-HT and PWV: ρ = 0.6, p < 0.001), its transporter (SERT and PWV: ρ = 0.5, p < 0.001), and the main indicators of arterial vascular stiffness. Our study revealed the relationship between high serotonin and SERT concentrations and markers of arterial stiffness. The results we obtained suggest the involvement of serotonin and SERT in the process of vascular remodeling in familial hypercholesterolemia in children.

5-hydroxytryphophan mitigates ergot alkaloid-induced suppression of serotonin and feed intake in cattle.

The impact of ergot toxicosis on livestock industries is detrimental and treatments are needed in many countries. The objective of this study was to evaluate the effects of acute exposure to ergot alkaloids and 5-hydroxytryptophan (5-HTP) supplementation on feed intake, serotonin metabolism, and blood metabolites in cattle. Eight Holstein steers (538 ± 18kg) fitted with ruminal cannulas were used in a replicated 4 × 4 Latin Square design experiment with a 2 × 2 factorial treatment structure. The treatments were the combination of 0 (E-) or 15 µg ergovaline/kg BW (E+) and 0 (5HTP-) or 0.5mg of 5-hydroxy-l-tryptophan/kg BW (5HTP+) administered daily for 6 d. Toxic endophyte-infected tall fescue seed was used to supply the daily dose of ergovaline. Endophyte-free seed was used to equalize seed intake between treatments. Ground seed was placed into the rumen immediately before feeding. The 5-HTP was dissolved in water and infused into the abomasum via the reticulo-omasal orifice. Blood was collected from a jugular vein catheter at 0, 1, 2, 4, 8, and 24h after treatment administration. Ergovaline without 5-HTP (E+/5HTP-) decreased dry matter intake (DMI) in comparison to steers without ergovaline and 5-HTP (E-/5HTP-). However, 5-HTP infusion in association with ergovaline (E+/5HTP+) normalized the DMI. Although E + did not affect (P > 0.05) the area under the curve (AUC) of serum 5-HTP, 5-hydroxyindoleacetic acid, tryptophan, and kynurenine, serum and plasma serotonin concentrations were decreased (P < 0.05). The infusion of 5-HTP increased (P < 0.05) the AUC of serum 5-HTP, serum and plasma serotonin, and serum 5-hydroxyindoleacetic acid. In conclusion, acute exposure to ergot alkaloids reduced DMI and circulating serotonin in cattle but 5-HTP administration showed potential to normalize both circulating serotonin and feed intake.

A randomized controlled trial to examine the impact of a multi-strain probiotic on self-reported indicators of depression, anxiety, mood, and associated biomarkers.

To examine the efficacy of supplementing with a multi-strain probiotic (MSP) on changes associated with mood, anxiety, and neurotransmitter levels. In a randomized, double-blind, placebo-controlled fashion, 70 healthy men and women (31.0 ± 9.5 years, 173.0 ± 10.4 cm, 73.9 ± 13.8 kg, 24.6 ± 3.5 kg/m2) supplemented with a single capsule of MSP (a total daily dose of 4 × 109 colony forming units [CFU] comprised of a 1 × 109 CFU dose from each of the following strains: Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01, and Bifidobacterium longum 04, Probiotical S.p.A., Novara, Italy) or a maltodextrin placebo (PLA). After 0, 2, 4, and 6 weeks of supplementation and 3 weeks after ceasing supplementation, study participants completed the Beck Depression Inventory (BDI-II), State-Trait Anxiety Inventory (STAI), and Leiden Index of Depression Sensitivity (LEIDS-R) questionnaires and had plasma concentrations of cortisol, dopamine, serotonin, and C-reactive protein determined. BDI, STAI, and total LEIDS-R scores were reduced from baseline (p < 0.05) with MSP supplementation after 4 and 6 weeks of supplementation and 3 weeks after supplementation while no changes (p > 0.05) were reported in PLA. When compared to PLA, MSP scores for state anxiety, trait anxiety, and LEIDS-R (hopeless, aggression, rumination, and total score) were significantly lower (p < 0.05) after supplementation. Plasma serotonin concentrations in MSP were increased from baseline after 6 weeks of supplementation and 3 weeks after ceasing supplementation. No changes (p > 0.05) in plasma dopamine, C-reactive protein, or cortisol concentrations were observed between groups. MSP supplementation resulted in widespread improvements in several questionnaires evaluating mood, anxiety, and depression in young, healthy men and women. MSP supplementation increased serotonin increased after 6 weeks of MSP supplementation with no change in dopamine, C-reactive protein, or cortisol. https://classic.clinicaltrials.gov/ct2/show/NCT05343533, NCT05343533.

Association between levels of serotonin, melatonin, cortisol and the clinical condition of patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic systemic connective tissue disease of autoimmune basis. It is characterized by inflammation of joints and systemic complications. The etiopathogenesis is still unknown. Predisposing factors for the disease include genetic, immunological and environmental. Chronic disease and the stress experienced by patients disrupt the body’s homeostatic state and weaken the human immune system. Reduced immunity and endocrine disruption may influence the development of autoimmune diseases and exacerbate their course. The aim of the study was to investigate whether there is a relationship between the blood levels of hormones such as cortisol, serotonin, melatonin and the clinical status of RA patients as determined by the DAS28 index and CRP protein. A total of 165 people participated in the study of these 84 subjects had RA and the rest were the control group. All participants completed a questionnaire and had their blood drawn to determine hormones. Patients with RA had higher plasma cortisol (324.6 ng/ml vs. 292.9 ng/ml) and serotonin concentrations (67.9 ng/ml vs. 22.1 ng/ml) and lower plasma melatonin (116.8 pg/ml vs. 330.2 pg/ml) compared to controls. Patients whose CRP concentration were above normal also had elevated plasma cortisol concentration. No significant association was observed in RA patients between plasma melatonin, serotonin and DAS28 values. However, it can be concluded that those with high disease activity had lower melatonin levels as compared to patients with low and moderate DAS28 values. Significant differences were found between RA patients not using steroids and plasma cortisol (p = 0.035). In RA patients, it was observed that as plasma cortisol concentration increased, the chance of having an elevated DAS28 score, indicating high disease activity, increased.

Blood serotonin concentration in children with COVID-19

COVID-19 has a risk of thrombotic complications. Serotonin plays an important role in pathogenesis of thrombosis.Purpose. To evaluate level of serotonin and its metabolite in the blood of children with COVID-19.Methods. This study included 72 children aged 3 to 17 years. Of these, 43 patients (mean age 11.2 ± 4.8 years) diagnosed with COVID-19 without comorbidities made up the study group, 29 healthy children (mean age 11.8 ± 3.8 years) — the control group. Concentration of serotonin and its metabolite (5-HIAA) in the blood was determined using high performance liquid chromatography with electrochemical detection. Computed tomography data were used to determine severity of lung damage.Results. In our study children with COVID-19 aged 3 to 17 years had significantly higher serotonin and its metabolite levels compared to the control group. Concentration of serotonin in plasma in main group was 20–30 times higher than in the same-age control. The 5-HIAA/serotonin ratio in children with COVID-19 is significantly lower than in the control group. Levels of serotonin and 5-HIAA in children with COVID-19 depending on the severity of CT-scan lung damage showed no significant differences.Conclusion. Serotonin and its metabolite levels in plasma of children with COVID-19 is significantly increased. It may be related to platelet hyperactivation in SARS-CoV-2 infection and increased risk of thrombosis, which requires further research.

The Role of Banana (Musa balbisiana Colla) Peel Floss as Functional Food Matrix to Alleviate Chronic Stress

BACKGROUND: Banana peel (Musa balbisiana Colla) already has a diverse variety of nutritional benefits, but its perishable nature necessitates additional food processing, one of which is banana peel floss.&#x0D; AIM: The objective of this study was to examine the antidepressant effects of banana peel floss in experimental animals subjected to chronic mild stress (CMS) for 6 weeks.&#x0D; METHODS: Animals were randomly assigned into five groups. The first group was fed a control diet without CMS as a negative control. The other four groups were exposed to CMS and fed a control diet as a positive control, with three of the five groups fed a control diet supplemented with 15%, 30%, and 60% banana peel floss. The tail suspension test (TST) and the Morris water maze were used as behavioral parameters in this study (MWM). Cortisol and serotonin levels were measured in two stages: after CMS exposure or before banana peel floss intervention, and after 4 weeks of banana peel floss intervention.&#x0D; RESULTS: The results showed that the immobility time in TST and escape latency in the MWM test were significantly reduced in the groups supplemented with 15% and 30% banana peel floss, respectively. Furthermore, we observed a significant association between serotonin and cortisol levels and also between the duration of immobility time in TST and serotonin levels.&#x0D; CONCLUSIONS: The administration of banana peel floss caused significant changes in plasma serotonin concentrations, implying that the presence of dietary fiber, tryptophan, and bioactive components in banana peel floss can reduce stress-induced depression by regulating cortisol levels and increasing serotonin levels.

Early Stepdown Weaning of Dairy Calves with Glutamine and Branched-Chain Amino Acid Supplementations.

Simple SummaryWe demonstrated previously that supplementation of glutamine (Gln) at 2.0% of dry matter intake (DMI) increased the rate at which dairy calves achieved ≥1.0 kg/d starter feed intake (SFI) during weaning. Because Gln supplements at <1.0% of DMI or branched-chain amino acid (BCAA) supplements have been shown to improve the performance of weaning piglets, we examined the effects of a lower dose of Gln (8.0 g/d equivalent to 1% of DMI) alone or in combination with BCAA supplementations on SFI and average daily gain (ADG) in this study. Amino acids did not affect SFI or ADG during the supplementations but decreased post-weaning SFI in an additive manner even though the ADG was not affected. The blood analysis on the last day of supplementations revealed a possibility for the Gln and BCAA supplementations to suppress SFI through leptin and serotonin secreted by the gastrointestinal tract.The study objective was to examine the effects of supplementing Gln and BCAA on the SFI and ADG of weaning dairy calves. Holstein heifer calves (11 calves /treatment) at 35 d of age were assigned to: (1) no amino acids (CTL), (2) Gln (8.0 g/d) alone (GLN), or (3) Gln (8.0 g/d) and BCAA (GLNB; 17.0, 10.0, and 11.0 g/d leucine, isoleucine, and valine, respectively) supplementations in whole milk during a stepdown weaning scheme. Calves were weaned completely once they achieved ≥1.0 kg/d SFI. Neither GLN nor GLNB affected SFI or ADG in the first week during weaning. The GLNB decreased SFI compared to CTL, but the SFI was similar between CTL and GLN in the remainder of the weaning scheme. All calves were weaned at 50 d of age. The SFI of GLNB was lower than that of GLN, and the SFI of both GLN and GLNB were lower than CTL post-weaning. The decreased SFI did not alter ADG during weaning or post-weaning. The GLNB tended to have higher plasma leptin and lower plasma serotonin concentrations compared to CTL. Glutamine and BCAA seem to affect the SFI of calves by modulating the secretions of endocrine cells in the gastrointestinal tract.

Serotonin assays in clinical practice. Do sex and activity play a role in serotonin concentrations in equine plasma?

Serotonin assays in clinical practice. Do sex and activity play a role in serotonin concentrations in equine plasma?

Clinical and diagnostic significance of endothelial dysfunction and serotonin levels in children with hemolytic-uremic syndrome

Hemolytic-uremic syndrome is a serious problem in pediatrics and pediatric nephrology. Hemolytic-uremic syndrome is one of the leading causes of acute kidney injury with potential transformation into terminal chronic kidney disease. Currently, the endothelial dysfunction is strongly associated with changes in the serotonergic system in the pathogenesis of hemolytic-uremic syndrome. There are few studies that have revealed an increase in the blood plasma serotonin concentration in children with hemolytic-uremic syndrome, but its role in the pathogenesis of chronic kidney disease has been insufficiently studied. The progressive course of hemolytic-uremic syndrome, up to the terminal stage of renal failure, requires the search for markers of renal tissue damage as prognostically significant factors for the development of nephrosclerosis, which is of particular importance for optimizing the management of such children.

Effects of dietary leucine and tryptophan on serotonin metabolism and growth performance of growing pigs.

An experiment was conducted to test the hypothesis that increased dietary Trp is needed in high-Leu diets for growing pigs to prevent a drop in plasma serotonin and hypothalamic serotonin concentrations and to maintain growth performance of animals. A total of 144 growing pigs (initial weight: 28.2 ± 1.9 kg) were assigned to 9 treatments in a randomized complete block design with 2 blocks, 2 pigs per pen, and 8 replicate pens per treatment. The 9 diets were formulated in a 3 × 3 factorial with 3 levels of dietary Leu (101%, 200%, or 299% standardized ileal digestible [SID] Leu:Lys), and 3 levels of dietary Trp (18%, 23%, or 28% SID Trp:Lys). A basal diet that met requirements for SID Leu and SID Trp was formulated and 8 additional diets were formulated by adding crystalline L-Leu and (or) L-Trp to the basal diet. Individual pig weights were recorded at the beginning of the experiment and at the conclusion of the 21-d experiment. On the last day of the experiment, 1 pig per pen was sacrificed, and blood and hypothalamus samples were collected to measure plasma urea N, plasma serotonin, and hypothalamic serotonin concentrations. Results indicated that increasing dietary Trp increased (P < 0.05) hypothalamic serotonin, whereas increases (P < 0.05) in average daily gain (ADG) and average daily feed intake (ADFI) were observed only in pigs fed diets containing excess Leu. Increasing dietary Leu reduced (P < 0.05) ADG, ADFI, and hypothalamic serotonin. However, the increase in ADG and ADFI caused by dietary Trp was greater if 299% SID Leu:Lys was provided than if 101% SID Leu:Lys was provided (interaction, P < 0.05). Plasma Leu concentration was positively affected by dietary Leu and negatively affected by dietary Trp, but the negative effect of Trp was greater if 299% SID Leu:Lys was provided than if 101% SID Leu:Lys was provided (interaction, P < 0.05). Plasma concentration of Trp was positively affected by increased dietary Trp and increased dietary Leu, but the increase in plasma concentration of Trp was greater if Leu level was at 101% SID Leu:Lys ratio than at 299% SID Leu:Lys ratio (interaction, P < 0.05). In conclusion, increased dietary Leu reduced ADG, ADFI, and hypothalamic serotonin concentration, and influenced metabolism of several indispensable amino acids, but Trp supplementation partly overcame the negative effect of excess Leu. This demonstrates the importance of Trp in regulation of hypothalamic serotonin, and therefore, feed intake of pigs.

Straw as an Alternative to Grass Forage in Horses-Effects on Post-Prandial Metabolic Profile, Energy Intake, Behaviour and Gastric Ulceration.

Simple SummaryMany leisure horses have low energy requirements and obesity is common. Straw has a low energy content and could be a forage option for these horses. However, a previous study suggested that providing straw as the only forage was associated with an increased risk for gastric ulcers. This study evaluated replacing 50% of the daily forage allowance with a good hygienic quality wheat straw. Six horses were fed both the control diet (grass forage only, CON) and the straw diet (50:50 grass forage and straw, S). Each diet was fed for three weeks and all horses were evaluated on both diets. Diet did not affect the prevalence of gastric ulcers. Feed intake time was longer and daily energy intake lower on diet S, compared to CON. Plasma insulin levels were lower on diet S compared to CON, which could be beneficial for horses with overweight or insulin dysregulation. The results suggest that good hygienic wheat straw provided at 50% of the forage ration does not cause gastric ulcers, but may prolong feeding time and promote a metabolic profile more suitable for overweight horses. Including straw as part of the ration therefore may improve welfare for horses with low energy requirements.Straw’s low energy content means it is a roughage option for horses with low energy requirements. Previously, in a field study, straw was associated with an increased risk for gastric ulcers. This study evaluated the effect on gastric ulcers, metabolic profile and behaviour of replacing, in a forage-only ration, 50% of the daily allowance with wheat straw. Six equines were studied in a 2 × 21-day cross-over design. The control diet (CON: 100% grass forage) and the straw diet (S: 50% grass forage and 50% straw [DM basis]) were iso-energetic. Gastroscopy was performed prior to the study and on day 21 and blood samples were collected and behavioural observations were performed. Diet did not affect squamous or glandular gastric ulcer scores (p > 0.05). Feed intake time was longer (p < 0.05) plus energy intake and plasma insulin concentrations were lower on diet S compared to CON (p < 0.0001). Plasma serotonin concentrations tended to be higher on diet S compared to CON (p = 0.05). The results suggest that good hygienic quality wheat straw can be included for up to 50% of the diet without causing gastric ulcers and that it can extend feeding time and promote a metabolic profile more suitable for overweight horses.

Assessment of Platelet and Plasma Serotonin in Canine Pulmonary Hypertension Secondary to Degenerative Mitral Valve Disease.

Background: Pulmonary hypertension (PH) is a common complication of degenerative mitral valve disease (DMVD), the most common cardiovascular disease in dogs. Serotonin has been suspected to play a role in the pathogenesis of PH, so this study aimed to investigate the differences in platelet and plasma serotonin between normal, DMVD and DMVD with PH (DMVD+PH) dogs.Materials and Methods: Sixty-two small-breed dogs were enrolled to the study and divided into the normal (n = 22), DMVD (n = 20), and DMVD+PH (n = 20) groups. The platelet and plasma serotonin concentrations were measured by the competitive ELISA.Results: The Kruskal–Wallis revealed the difference among the four groups of normal (179.73 [102.37–352.24] ng/109 platelets), DMVD (325.99 [96.84–407.66] ng/109 platelets), DMVD with intermediate probability of PH (291.11 [106.69–400.84] ng/109 platelets) and DMVD with high probability of PH (35.82 [2.69–126.35] ng/109 platelets) (p = 0.014). The Dunn's post-hoc test showed a decrease in the platelet serotonin concentration of the DMVD dogs with high probability of PH compared to the DMVD group (p = 0.008). The plasma serotonin concentration was not different between normal, DMVD, and DMVD+PH dogs.Conclusion: In conclusion, a decrease in platelet serotonin concentration, which is associated with a degree of PH probability was found in DMVD dogs with PH. Further studies investigating roles of platelet serotonin in PH secondary to DMVD should be performed.

The Effects of Androstenone on the Plasma Serotonin, β-Endorphin, and Cortisol Concentrations in Thoroughbred Horses.

Simple SummaryThe development of horse managing tools is needed to prevent accidents and to improve welfare for domestic horses because the safety hazards for people who are exposed to horses are well documented. Androstenone, a pheromone secreted from boars, changes the behavior of dogs to become less excited. In horses, a previous study showed that a specific receptor for androstenone was expressed in the vomeronasal organ and nasal cavity. Horses treated with androstenone also showed more compliant behaviors. Thus, this study was conducted to investigate the mechanism of androstenone for changing horse behaviors. The change in the plasma concentrations of serotonin, β-endorphin, and cortisol in response to the treatment of androstenone was evaluated using an immunoassay. The results of this study demonstrated that androstenone may control the neuroendocrine system of horses, resulting in behavioral changes. This is the first work that studies the mechanism of pheromone treatment in horses and can be applied for further study about the effect of pheromone therapy on horses.Androstenone influences the changing behaviors of animals. Previous studies discovered that an androstenone receptor was expressed in horses and treatment with androstenone induced horses to be more compliant. As changes in the level of neuroendocrine factors result in animal behavioral changes, the objective of the study was to monitor the changes in the concentrations of 5-HT, β-endorphin, and cortisol in response to androstenone. Eight thoroughbred horses (five mares and three geldings) were treated with androstenone diluted in jojoba oil (10 µg/mL) and only oil for a control cross-overly. A handler applied the treatments to the horses′ nostril and rubbed for 5 s. Blood samples were collected before, 15, 30, and 60 min after each treatment. The concentrations of each neurotransmitter were analyzed by enzyme-linked immunosorbent assay. The concentrations of each neurotransmitter after the treatment were compared to its baseline concentration. The concentration of 5-HT of the androstenone-treated horses remained consistent throughout the experiment, while the concentration of the control group significantly decreased over time. The plasma concentration of β-endorphin in the androstenone-treated group also remained constant, whereas the concentration increased in the control group. Cortisol levels did not change in either the treated or untreated groups. An androstenone treatment triggers changes in the secretion of 5-HT and β-endorphin in horses.

The influence of whole body cryotherapy on plasma concentration of melatonin and serotonin in patients with osteoarthrosis of the lumbar spine

Background: ‪Osteoarthrosis (OA) is the most common disease affecting mankind. There are many physiotherapeutic methods of treating OA symptoms. One of them is whole body cryotherapy (WBCT). The aim of this study was to present the impact of WBCT combined with kinesiotherapy on functional efficiency and changes in plasma concentrations of serotonin and melatonin in patients with lumbar spine OA.. Material and methods: ‪60 patients underwent a series of WBCT combined with kinesiotherapy (group A). 60 patients underwent a series of kinesiotherapy alone (group B). Before and after the therapy patients were examined by Rolland Morris Disability Questionnaire (RMDQ), and blood samples were collected for laboratory assessment. Results: ‪Following therapy, the functional efficiency (RMDQ) improved by 33% in both study groups (p &lt; 0.0001). After the therapy, both in the group of patients undergoing WBCT combined with exercises (group A, p = 0.032) and the cryotherapy alone (group B, p &lt; 0.0001), the plasma melatonin concentration significantly increased. The rise of plasma serotonin concentrations was higher in group B as compared to group A, but in both study groups the increase in plasma serotonin was statistically significant (p &lt; 0.0001).. Conclusions: ‪WBCT combined with therapeutic exercises as well as kinesiotherapy used alone resulted in an increase in melatonin and serotonin plasma levels and an improvement in functional efficiency in patients with lumbar spine OA.

ERICH3: vesicular association and antidepressant treatment response

Selective serotonin reuptake inhibitors (SSRIs) are standard of care for major depressive disorder (MDD) pharmacotherapy, but only approximately half of these patients remit on SSRI therapy. Our previous genome-wide association study identified a single-nucleotide polymorphism (SNP) signal across the glutamate-rich 3 (ERICH3) gene that was nearly genome-wide significantly associated with plasma serotonin (5-HT) concentrations, which were themselves associated with SSRI response for MDD patients enrolled in the Mayo Clinic PGRN-AMPS SSRI trial. In this study, we performed a meta-analysis which demonstrated that those SNPs were significantly associated with SSRI treatment outcomes in four independent MDD trials. However, the function of ERICH3 and molecular mechanism(s) by which it might be associated with plasma 5-HT concentrations and SSRI clinical response remained unclear. Therefore, we characterized the human ERICH3 gene functionally and identified ERICH3 mRNA transcripts and protein isoforms that are highly expressed in central nervous system cells. Coimmunoprecipitation identified a series of ERICH3 interacting proteins including clathrin heavy chain which are known to play a role in vesicular function. Immunofluorescence showed ERICH3 colocalization with 5-HT in vesicle-like structures, and ERICH3 knock-out dramatically decreased 5-HT staining in SK-N-SH cells as well as 5-HT concentrations in the culture media and cell lysates without changing the expression of 5-HT synthesizing or metabolizing enzymes. Finally, immunofluorescence also showed ERICH3 colocalization with dopamine in human iPSC-derived neurons. These results suggest that ERICH3 may play a significant role in vesicular function in serotonergic and other neuronal cell types, which might help explain its association with antidepressant treatment response.

Sweet Taste Antagonist Lactisole Administered in Combination with Sucrose, But Not Glucose, Increases Energy Intake and Decreases Peripheral Serotonin in Male Subjects.

Knowledge regarding the involvement of sweetness perception on energy intake is scarce. Here, the impact of glucose and sucrose sweetness, beyond their caloric load, on subsequent food intake and biomarkers of satiation was evaluated by co-administration of the sweet taste receptor inhibitor lactisole. A total of 27 healthy, male subjects received solutions of either 10% glucose w/o 60 ppm lactisole or 10% sucrose w/o 60 ppm lactisole. Subsequent food intake from a standardized breakfast was evaluated 2 h after receiving the respective test solution. Changes in postprandial plasma concentrations of cholecystokinin, ghrelin, and serotonin were determined over a period of 120 min, as was the body temperature. Administration of lactisole to the sucrose solution increased the energy intake from the subsequent standardized breakfast by 12.9 ± 5.8% (p = 0.04), led to a decreased Δ AUC of the body core temperature by 46 ± 20% (p = 0.01), and time-dependently reduced Δ serotonin plasma concentrations (−16.9 ± 6.06 ng/mL vs. −0.56 ± 3.7 ng/mL after sucrose administration, p = 0.03). The present study shows that lactisole increases energy intake and decreases plasma serotonin concentrations as well as body core temperature induced by sucrose, but not glucose. This finding may be associated with the different binding affinities of sucrose and glucose to the sweet taste receptor.

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.