Platelet Serotonin Research Articles

Role of platelet serotonin in innate immune cell recruitment.

Serotonin (5-Hydroxytryptamine, 5-HT) was discovered as a vasoconstrictor in 1937. Since its discovery, the involvement of serotonin in numerous physiological processes was described. It acts as an important neurotransmitter, regulates bowel movement, can be released as a tissue hormone and acts as a growth factor. Among the years, a link between serotonin and inflammation has been identified and further evidence suggests an important role of serotonergic components in immune responses. Peripheral serotonin is synthesized by the enzyme tryptophan hydroxylase (Tph), which exists in two different isoforms: Tph2 being responsible for serotonin synthesis in neurons and Tph1 for generation of serotonin in peripheral organs. After synthesis in intestinal enterochromaffin cells, serotonin is stored in platelets and released upon stimulation. Several immune cells express the serotonin transporter SERT and enzymes for serotonin metabolism (monoamine oxygenase, MAO). To be susceptible to changes in serotonin levels, serotonin receptors are required and almost all of the 15 receptor subtypes are represented on immune cells. In this review, we describe the distribution of serotonergic components in cells of the immune system and the impact of platelet-derived serotonin on these cells. In particular, we aim to understand the effect of serotonin on immune cell recruitment to sites of inflammation.

Modern approaches to objectivization of diagnostics of mental disorders

586 patients with mental disorders of headings F0-F4 (according to the 10th revision of the International Statistical Classification of Diseases) and 18 mentally healthy people were studied. An automated ethological analysis of psychodiagnostic interviews, an enzyme-linked immunosorbent assay, a pictographic survey, psychometric scales, stress testing, and structural and functional neuroimaging methods were used. Reliable differences are shown when examining patients with mental disorders using a set of instrumental, laboratory and psychophysiological methods for investigating mental disorders. Significant differences in the volume of behavioral reactions in patients with schizophrenic disorder were revealed. With the help of the pictographic methodic, reliable differences are shown in patients with neurotic disorders and depressive episodes, as well as in persons with preclinical neurotic disorders. Neuroimaging methodic showed significant differences in the structure and functional activity of different parts of the brain in patients with endogenous, organic, neurotic depressions, as well as addictive disorders compared with healthy individuals. It was found that, despite the pronounced individual differences, even a simple comparative analysis (ethological part of the study) revealed statistically significant indicators in the volume of behavioral reactions in patients with schizophrenia spectrum disorders, compared with healthy individuals. The results of the study of «neuroimaging markers» of the depressive disorders have shown, that «endogenous» depression at the PET (positron emission tomography) - study was determined by the decrease in the level of metabolism in the heads of caudate nuclei by20-40% of normal with moderate depression (up to 25 points on the HAMD) and more than 40% - severe (more than 26 points on the HAMD) compared to the control group, which was not observed in the «reactive» depression. It was found that the use of «neuroendocrine markers» (platelet serotonin, cortisol) in the diagnosis of depressive disorders allows, on the one hand, to study the causal mechanisms of mental disorders with an externally similar phenomenological picture, and on the other - to assess the pathophysiological consequences and severity of mental pathology. The possibility of modification of approaches to objectification, prognosis and early detection of mental disorders is shown.

Evidence that ITGB3 promoter variants increase serotonin blood levels by regulating platelet serotonin transporter trafficking.

Elevated serotonin (5-HT) blood levels, the first biomarker identified in autism research, has been consistently found in 20-30% of patients with Autism Spectrum Disorder (ASD). Hyperserotonemia is mainly due to greater 5-HT uptake into platelets, mediated by the 5-HT transporter (SERT) located at the platelet plasma membrane. The protein complex involved in platelet SERT trafficking and externalization includes integrin β3, the beta subunit of the platelet membrane adhesive GP IIb/IIIa. Integrin β3 is encoded by the ITGB3 gene, previously identified as a quantitative trait locus (QTL) for 5-HT blood levels in ASD at single nucleotide polymorphism (SNP) rs2317385. The present study aims to identify the functional ITGB3 gene variants contributing to hyperserotonemia. ITGB3 gene sequencing in 20 individuals selected on the basis of rs2317385 genotypes defined four haplotypes encompassing six SNPs located in the ITGB3 gene promoter region, all in linkage disequilibrium with rs2317385. Luciferase assays in two hematopoietic cell lines, K-562 and HEL 92.1.7, demonstrate that ITGB3 gene promoter activity is enhanced by the presence of the C allele at rs55827077 specifically during differentiation into megakaryocytes (P<0.01), with modulatory effects by flanking SNPs. This same allele is strongly associated with (a) higher 5-HT blood levels in 176 autistic individuals (P<0.001), (b) greater platelet integrin β3 protein expression (P<0.05) and (c) enhanced SERT trafficking from the cytosol toward the platelet plasma membrane (P=4.05×10-11). Our results support rs55827077 as the functional ITGB3 gene promoter variant contributing to elevated 5-HT blood levels in ASD and define a mechanistic chain of events linking ITGB3 to hyperserotonemia.

Variables affecting the potential efficacy of PRP in providing chronic pain relief.

Although chronic pain affects about 1% of the US population, it remains largely resistant to treatment. Despite great variability in pain outcomes, the application of autologous platelet-rich plasma (PRP) has become increasingly popular in attempts to reduce chronic pain. The variability in PRP efficacy raises the question of whether PRP actually has an analgesic capacity, and if so, can that capacity be made consistent and maximized. The best explanation for the variability in PRP analgesic efficacy is the failure during PRP preparation and application to take into account variables that can increase or eliminate its analgesic capabilities. This suggests that if the variables are reduced and controlled, a PRP preparation and application protocol can be developed leading to PRP inducing reliable, complete, and long-term pain relief. The goal of this study was to examine some of the variables that influence platelets and see how they might be controlled to increase the analgesic potential of PRP. Among the variables examined are the physiological status of the patient, methods used to prepare PRP, and methods of PRP application. The goal of modifying these variables is to minimize platelet serotonin content, maximize platelet content of factors that reduce inflammation and pain, while maintaining their bioactivity, maximize platelet capacity to aggregate at injury sites, induce rapid and simultaneous release of their contents, and optimize PRP application protocols. It is concluded that controlling some or many of these variables will lead to PRP that induces reliable, maximum, and long-term relief of chronic pain.

Echogenic alteration in the raphe nuclei measured by transcranial sonography in patients with Parkinson disease and depression.

Background:Recently, several studies using transcranial sonography (TCS) have demonstrated reduced echogenicity of the mesencephalic midline in unipolar depression and patients with comorbid depression and Parkinson disease (PD). However, there is no consensus on the conclusion that raphe nuclei (RN) hypoechogenicity is associated with depression in PD. The methods used in previous studies lack quantitative and objective indicators to some extent; therefore, the present study used the level of platelet 5-hydroxytryptamine (5-HT) as an objective indicator of depression. Additionally, the reason for the reduced echogenicity of the brainstem raphe is still unclear.Objectives:The purpose of the present study was to assess the correlation between alterations in RN echogenicity and depressive symptoms in patients with PD using transcranial sonography (TCS). This information could provide a meaningful clinical reference for the antidiastole between depressive symptoms in PD and unipolar depression in patients with PD in whom depressive symptoms occur before motor symptoms.Methods:TCS was performed in patients with PD, patients with PD and depression, patients with depression and no PD, and healthy controls. Using the red nucleus as a reference, the RN was rated from grades 0 to 1 (grade 0: invisible, slightly echogenic, or interrupted RN; grade 1: hyperechogenicity in the RN observed as a continuous line).Results:The rate of abnormal RN (grade 0) was found to be 16.67% in patients with PD (5/30) and 14.29% in healthy controls (4/28). The presence of abnormal RN was significantly higher (χ2 = 15.983, P < .05) in patients with depression and PD (40%, 12/30) and in patients with depression only (58.33%, 14/24) than in those without depression and healthy controls. No correlation was found between RN changes and depression severity (P > .05). There were no statistical differences in the concentration of platelet serotonin among the 4 groups (P > .05).Conclusions:TCS of the mesencephalic midline may be useful for detecting depression, which is an early symptom of PD. However, further neuropathological studies are needed to understand the principles underlying the use of platelet serotonin as a peripheral biomarker, as well as the connection between PD and depression.

Are Platelet Aggregation Tests the Best Way to Assess New Drugs for Arterial Disease

Over many years, laboratory testing of platelet aggregability have been carried out in attempts to develop drugs that would prevent thrombosis in arteries. The problems encountered included the question of methodology. Blood samples have to be anticoagulated in order to study the platelets. Anti-coagulation with citrate and tests on derived platelet rich plasma did not correlate at all well with thrombus growth in the stenosed coronary arteries of experimental animals and citrate removes the calcium ions which are vital for platelet function. Anticoagulation with heparin also interfered with platelet function, so that now, hirudins are the preferred anticoagulant. However it was observed that if, instead of stimulating platelet aggregation with adrenaline or ADP, serotonin was applied to the preparation, very little aggregation took place in spite of serotonin 5HT2A antagonists being the most potent inhibitors of thrombus growth in experimental animals. Another indicator that primary platelet agggregation is not a predictor of in vivo efficacy was the finding that 5HT2A antagonism inhibited aggregate growth. In a stenosed artery the platelets are activated by increased shear stress and blood turbulence with release of platelet serotonin causing positive feedback activation of more platelets. At present, there does not seem to be a bench in vitro test that accurately predicts in vivo efficacy in stenosed artery occlusive thrombosis.

Platelet serotonin and serotonin transporter as peripheral surrogates in depression and anxiety patients

Previous studies suggested that serotonergic neurons and platelets share similarities in serotonin (5-HT) uptake by serotonin transporter (SERT), storage, metabolism and release mechanisms, indicating that platelets may be used as a reliable peripheral surrogate to measure central SERT activity in neuropsychiatric research. In this study, platelet 5-HT content and 5-HT uptake capacity of SERT in depression and anxiety patients were measured by ELISA and flow cytometry with IDT307 at baseline and after serotonin reuptake inhibitors (SSRIs) treatment for 4 weeks. Healthy persons matched with age and gender were used as reference. The clinical presentations of the patients were assessed with Hamilton Depression (HAMD) and Anxiety Rating Scales (HAMA) at the same time points. Compared to healthy subjects, anxiety and depression patients showed higher levels of platelet 5-HT and IDT307 fluorescence intensity, but the values were comparable between the patient groups. SSRIs administration for 4 weeks significantly decreased scores of HAMD (29 vs 14) and HAMA (22 vs 14) in depression and anxiety patients, respectively; while it decreased platelet 5-HT content, but did not change the IDT307 fluorescence intensity of platelets. After incubation with fluoxetine in vitro, the IDT307 fluorescence intensity of isolated platelets from both healthy subjects and patients decreased in a dose-dependent manner. These results provide further evidence supporting the employment of platelet 5-HT content and SERT as peripheral surrogates in depression and anxiety patients, and are of help in understanding the several weeks’ delay from the initiation of antidepressant medication to their full therapeutic effects in the patients.

Association of Platelet Count and Platelet Transfusion With Serotonin Level During Living Donor Liver Transplantation: Possible Connection to Graft Regeneration

BackgroundWe recently showed that platelet counts and the amount of platelet transfusion during liver transplantation are positively associated with early graft regeneration. It was hypothesized that platelet-derived serotonin mediates liver regeneration. ObjectivesThis study aimed to evaluate the association between intraoperative platelet count, platelet transfusion, and serum serotonin level. MethodsThirty-two recipients undergoing living-donor liver transplantation were enrolled into this prospective observational study. Serum platelet counts and serotonin levels were measured at the following times: anesthetic induction, start of the anhepatic phase, before graft reperfusion, 5 minutes/1 hour/3 hours/5 hours after graft reperfusion, and before/after platelet transfusion. Serotonin was measured by using a liquid chromatography tandem mass spectrometry. ResultsSerotonin level at the anesthetic induction was 24.5 μg/mL (interquartile range, 14.6 to 38.1 μg/mL). During surgery, serial changes in platelet counts and serotonin levels showed a similar trend: they decreased during the anhepatic phase, increased during the first hour after graft reperfusion, and thereafter gradually decreased. Serotonin level was positively correlated with platelet counts (correlation coefficient = 0.620, P < .001). Allogeneic platelet transfusion significantly increased platelet count from 22 (19–31) × 109/L to 53 (50–81) × 109/L (P = .008) and it also increased serum serotonin from 11.04 (6.41–15.34) μg/mL to 34.26 (25.86–41.94) μg/mL (P = .008). ConclusionsOur findings indicate that allogeneic platelets could act as effector cells deriving serotonins. Also, our findings support the hypothesis that the association between platelets and post-transplantation graft regeneration is mediated by serotonin. Further studies are warranted regarding the respective role of serotonin and other platelet-derived molecules mediating liver regeneration.

The Serotonin Transporter Gene Polymorphisms and Risk of Ischemic Stroke

Introduction: Serotonin is known as a neurotransmitter; however, it also plays an important role in platelet aggregation as it is released upon platelet activation. The serotonin transporter (SERT) is responsible for the uptake of serotonin into platelets. Functional polymorphisms in the SERT gene may influence platelet activity, as they result in different levels of transporters and thereby different levels of serotonin in platelets. SERT gene polymorphisms have thus been associated with the risk of myocardial infarction. A similar association may exist between SERT gene polymorphisms and stroke. However, to our knowledge, this potential association has not previously been studied. We therefore aimed to investigate the association between polymorphisms in the SERT gene and the risk of ischemic stroke/transitory ischemic attack (TIA). Materials and Methods: We conducted a case-control study including 834 consecutively admitted first-ever Caucasian ischemic stroke patients/TIA from Aarhus University Hospital, Denmark and 571 healthy controls. The control group comprised a sample from the Danish working population, who were all employees in the public sector in the Central Denmark Region. Two polymorphisms, the length variation (short = S/long = L) in the serotonin-transporter-linked polymorphic region and a single-nucleotide (A/G) polymorphism (rs25531) were studied. The genotypes were grouped according to the functional activity: SS, SLG and LGLG (low expression), SLA, LGLA (medium expression), and LALA (high expression). Data were analyzed using logistic regression and results presented as OR with 95% CI. Results: The high-expression genotype was associated with a lower risk of ischemic stroke/TIA when compared to both the medium expression genotype (OR 0.72, 95% CI 0.56–0.93) and the low-expression genotype (OR 0.75, 95% CI 0.55–1.01) as well as the combination of the low and medium expression genotypes (OR 0.73, 95% CI 0.58–0.93). The lower OR estimates associated with the high-expression genotype were consistent across all stroke subtypes, although not statistically significant. The results remained virtually unchanged, although not reaching statistical significance, when adjusting for age and gender. Conclusion: The presence of the high expression SERT genotype (LALA) may be associated with a lower risk of ischemic stroke/TIA. This is, to our knowledge, the first study examining the SERT gene polymorphisms and the risk of stroke. The present results raise interesting considerations for future personalized medicine potential, and we argue that further larger-scale studies with sufficient power to study subgroups according to stroke etiology and stroke-onset age are needed.

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.

Feasibility of Conducting Autism Biomarker Research in the Clinical Setting.

Recruitment and completion of research activities during regular clinical care has the potential to increase research participation in complex neurodevelopmental disorders. We evaluated the feasibility, and effect on clinical care, of conducting biomarker research within a subspecialty clinical visit for autism spectrum disorder (ASD). Children, aged 5 to 10 years, were recruited by providers in ASD clinics at 5 institutions. Biomarkers collected were growth measurements, head circumference, neurologic and dysmorphology examinations, digit ratio (2D:4D) measurement, and platelet serotonin and urinary melatonin sulfate excretion levels. Parents completed the Aberrant Behavior Checklist-Community and a medical/demographic questionnaire. Cognitive level was abstracted from the medical record. Parents and clinicians completed surveys on the effect of the study on the clinical visit. Eighty-three children and their caregivers participated. Factors limiting participation included difficulty reaching families by phone and parent concern about the study blood draw requirement. All children completed at least 4 of 7 planned research activities. Demographic factors, educational placement, and child behavior were not associated with completion of study activities. Lower nonverbal cognitive function was weakly associated with fewer activities completed. Forty-four percent of clinicians reported an effect of the research study on the clinical visit. However, neither parent-reported nor clinician-reported effect was associated with the degree of study activity completion. Recruiting study participants in the context of scheduled ASD clinical visits required significant effort. However, once recruited, participants completed most study activities, regardless of behavioral symptom severity. Research activities did not adversely affect the clinical visit.

Inhibition of Collagen-Induced Platelet Aggregation by the Secobutanolide Secolincomolide A from Lindera obtusiloba Blume.

Atherothrombosis is one of the main underlying cause of cardiovascular diseases. In addition to treating atherothrombosis with antithrombotic agents, there is growing interest in the role of natural food products and biologically active ingredients for the prevention and treatment of cardiovascular diseases. This study aimed to investigate the effect of secolincomolide A (3) isolated from Lindera obtusiloba Blume on platelet activity and identify possible signaling pathways. In our study, the antiplatelet activities of 3 were measured by collagen-induced platelet aggregation and serotonin secretion in freshly isolated rabbit platelets. Interestingly, 3 effectively inhibited the collagen-induced platelet aggregation and serotonin secretion via decreased production of diacylglycerol, arachidonic acid, and cyclooxygenase-mediated metabolites such as thromboxane B2 (TXB2), and prostaglandin D2 (PGD2). In accordance with the antiplatelet activities, 3 prolonged bleeding time and attenuated FeCl3-induced thrombus formation in arterial thrombosis model. Notably, 3 abolished the phosphorylation of phospholipase Cγ2 (PLCγ2), spleen tyrosine kinase (Syk), p47, extracellular signal-regulated kinase 1/2 (ERK1/2), protein kinase B (Akt) by inhibiting the activation of the collagen receptor, glycoprotein VI (GPVI). Taken together, our results indicate the therapeutic potential of 3 in antiplatelet action through inhibition of the GPVI-mediated signaling pathway and the COX-1-mediated AA metabolic pathways.

Suicide risk is associated with low levels of platelet serotonin in bipolar I disorder

Suicide risk is associated with low levels of platelet serotonin in bipolar I disorder

Improved strength on 5-hydroxytryptophan and carbidopa in spinal cord atrophy

There is ample evidence of an important role of descending serotonergic projections in modulating spinal motor neuron activation and firing, and experimental studies suggest that 5-HT receptor stimulation can improve motor function after spinal cord injury; however, relevant clinical data is sorely lacking. We describe two sisters with hemiplegic migraine, low CSF and platelet serotonin levels, and progressive spastic paraparesis associated with profound spinal cord atrophy whose lower extremity strength and ambulation responded to a precursor replacement strategy (5-hydroxytryptophan and carbidopa administration), an approach that may have broader applicability in myelopathies of diverse etiology where descending serotonergic projections are compromised.

Platelet Serotonin Level and Impulsivity in Human Self-destructive Behavior: A Biological and Psychological Study.

Context:Suicide is a disease and a global public health problem. Suicidology has come to become a topic of study for intervention and research. The serotonin (5-hydroxytryptamine [5HT]) system has remained a prime area of investigation. The neurons and platelets display structural and functional similarities. Ninety-nine percent of 5HT is contained in platelets, which shares similar 5HT uptake and release mechanisms with 5HT neurons.Aims:This study aims to study human self-destructive behavior (HSDB).Objectives:Exploring the biological (serotonin levels in platelets) and psychological aspects (impulsivity) of attempted suicide or HSDB.Settings and Design:Thirty-one patients, above the age of 18 years, with a recent history of HSDB, were studied and given an International Classification of Diseases-10 diagnosis, after a detailed interview.Subjects and Methods:For the platelet 5HT estimation, blood samples were collected, and enzyme immunometric assay carried out. Detailed assessment of the impulsivity was done by the 25-item structured diagnostic interview for borderlines by Zanarini et al.Statistical Analysis Used:We obtained both categorical and continuous data. Chi-square test, Fisher's test, Student's t-test, and Pearson's product moment correlation were used.Results:Female subjects outnumbered males by 2:1. Major depression, adjustment disorder, personality disorder were predominant diagnoses. The mean platelet serotonin concentration for males = 57.3 ng/ml, that of females = 56.05 ng/ml (P > 0.05). Platelet 5HT levels were found to be negatively correlated with impulsivity scores (P < 0.05).Conclusions:Platelet serotonin levels in our study sample were quite low when compared with those reported in published literature. Low serotonin levels were inversely related to impulsivity, but only in males.

Platelet Alpha-Storage Pool Defect Combined with Non-Classic Delta-Storage Pool Deficiency - with a Severe Bleeding Tendency

Aims:We report about a 35 year old male patient with severe and frequent epistaxis and hematoma since infancy. He presented with mild thrombocytopenia and increased mean platelet volume. Von Willebrand's disease and subhemophilia had been excluded. Previously, he was diagnosed with immune thrombocytopenic purpura. He never underwent elective surgery. His parents were asymptomatic. However, his young daughter also suffers from severe bleeding symptoms and was referred to our coagulation outpatient clinic to investigate the bleeding disorder.Methods:Platelet function was assessed by light transmission-, lumi-aggregometry and flow cytometry. Lysates of gel-filtered platelets were analyzed for total granule P-selectin, CD63 and von Willebrand factor (VWF) content by Western blotting and for serotonin levels by ELISA, respectively. Molecular genetic analysis was performed using whole exome sequencing and pyrosequencing.Results: Platelet aggregation in response to ADP was not inducible. Platelet aggregation in response to epinephrine resulted in monophasic curves. Platelet aggregation in response to TRAP-6 or collagen was inducible but impaired and accompanied by disaggregation. In contrast, arachidonic acid- and U46619-induced platelet aggregation as well as ristocetin-induced platelet agglutination/aggregation was within the normal range. Also platelet surface expression of GPIIb/IIIa, GPIb/V/IX, GPVI and CD29 was normal. Activation of GPIIb/IIIa in response to ADP, convulxin or TRAP-6 was inducible but diminished and in response to epinephrine or arachidonic acid normal. P-selectin (alpha-granule marker) and CD63 (dense body/lysosome marker) surface expression was not inducible by thrombin or convulxin and markedly reduced in response to TRAP-6 and arachidonic acid. Immunoblot analysis of isolated platelets demonstrated pronouncedly decreased content of total P-selectin, VWF and CD63. Fluorescent staining of adenine nucleotides by mepacrine in patient’s platelet dense bodies and secretion of ATP induced by arachidonic acid (normal aggregation) were absent. However, patient’s platelet serotonin levels were within the normal range. The molecular genetic diagnostic showed an undescribed mutation in the GATA1 gene (c.886A>C hemizygot, p.T296P). The bioinformatic check confirmed a pathogenetic importance of this mutation located in the domain I of the C-terminal zinc finger.Conclusion: We describe the first case of a combined platelet alpha- and partial delta-storage pool disorder where the dense granules lack adenine nucleotides but contain normal levels of serotonin - causing a severe bleeding disorder. DisclosuresNo relevant conflicts of interest to declare.

Antiplatelet and antithrombotic effects of cordycepin-enriched WIB-801CE from Cordyceps militaris ex vivo, in vivo, and in vitro.

BackgroundA species of the fungal genus Cordyceps has been used as a complementary and alternative medicine of traditional Chinese medicine, and its major component cordycepin and cordycepin-enriched WIB-801CE are known to have antiplatelet effects in vitro. However, it is unknown whether they have also endogenous antiplatelet and antithrombotic effects. In this study, to resolve these doubts, we prepared cordycepin-enriched WIB-801CE, an ethanol extract from Cordyceps militaris-hypha, then evaluated its ex vivo, in vivo, and in vitro antiplatelet and antithrombotic effects.MethodsEx vivo effects of WIB-801CE on collagen- and ADP-induced platelet aggregation, serotonin release, thromboxane A2 (TXA2) production and its associated activities of enzymes [cyclooxygenase-1 (COX-1), TXA2 synthase (TXAS)], arachidonic acid (AA) release and its associated phosphorylation of phospholipase Cβ3, phospholipase Cγ2 or cytosolic phospholipase A2, mitogen-activated protein kinase (MAPK) [p38 MAPK, extracellular signal-regulated kinase (ERK)], and blood coagulation time in rats were investigated. In vivo effects of WIB-801CE on collagen plus epinephrine-induced acute pulmonary thromboembolism, and tail bleeding time in mice were also inquired. In vitro effects of WIB-801CE on cytotoxicity, and fibrin clot retraction in human platelets, and nitric oxide (NO) production in RAW264.7 cells or free radical scavenging activity were studied.ResultsCordycepin-enriched WIB-801CE inhibited ex vivo platelet aggregation, TXA2 production, AA release, TXAS activity, serotonin release, and p38 MAPK and ERK2 phosphorylation in collagen- and ADP-activated rat platelets without affecting blood coagulation. Furthermore, WIB-801CE manifested in vivo inhibitory effect on collagen plus epinephrine-induced pulmonary thromboembolism mice model. WIB-801CE inhibited in vitro NO production and fibrin clot retraction, but elevated free radical scavenging activity without affecting cytotoxicity against human platelets.ConclusionWIB-801CE inhibited collagen- and ADP-induced platelet activation and its associated thrombus formation ex vivo and in vivo. These were resulted from down-regulation of TXA2 production and its related AA release and TXAS activity, and p38 MAPK and ERK2 activation. These results suggest that WIB-801CE has therapeutic potential to treat platelet activation-mediated thrombotic diseases in vivo.

Changes in EEG indices and serotonin concentrations in depression and anxiety disorders

Electroencephalogram (EEG) is an important tool to study brain function. EEG can evaluate the current functional state of the brain with high temporal resolution and identify metabolic and ion disorders that cannot be detected by magnetic resonance imaging. Objective: to analyze the relationship between some neurophysiological and biochemical parameters with a Neuro-KM hardware-software complex for the topographic mapping of brain electrical activity. Patients and methods. 75 patients with depression, 101 with anxiety disorders (AD), and 86 control individuals were examined. EEG spectrum and coherence changes were estimated in the depression and AD groups versus the control group. Correlation analysis of EEG indices and blood serotonin concentrations was carried out. Results and discussion. The patients with depression and those with AD as compared to the controls were observed to have similar EEG spectral changes in the beta band. Coherence analysis in the beta-band showed that both disease groups versus the control group had oppositely directed changes: a reduction in intra- and interhemispheric coherence for depression and its increase for AD (p < 0.001). That in the theta and alpha bands revealed that both disease groups had unidirectional interhemispheric coherence changes: a decrease in integration in the alpha band and its increase in the theta and delta bands in the depression and AD groups (p < 0.05) and multidirectional changes in intrahemispheric coherence: its reduction in the depression group and an increase in the AD group (p < 0.05). Correlation analysis of EEG parameters and platelet serotonin concentrations showed opposite correlations of serotonin concentrations and EEG percentage power in the theta and beta bands. When there were higher serotonin concentrations in the patients with depression, EEG demonstrated a preponderance of a synchronization pattern; when these were in the patients with AD, there was a predominance of a desynchronization pattern. Conclusion. The specific features of EEG in the depression and AD groups may indicate serotonin metabolic disorders and the efficiency of therapy with selective serotonin reuptake inhibitors.

P.2.f.027 - Efficacy of vortioxetine versus other antidepressants on cognitive dysfunction in patients with major depressive disorder

The discovery of serotonin in platelets in the 1950s heralded a new era of research in the study of blood clot formation. Platelets, which represent the cellular components in the blood responsible for initiating blood clot formation, are responsible for maintaining a low concentration of plasma serotonin by sequestering and storing a remarkable concentration of serotonin. While platelets are vital for regulating circulating serotonin levels in the plasma, serotonin itself is suggested to play a fundamental role in both platelet function and blood clot formation. However, despite many studies, the role for serotonin in thrombus formation is still not completely elucidated. This chapter will explore a brief history of both platelets and serotonin and present a current understanding of the interactions between the two. Here we discuss the vital role of platelets in the regulation of circulating serotonin concentrations, the significant role of serotonin in platelets for the hemostatic and thrombotic responses, and the clinical implications of modulating this process in health and disease.