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Biomolecules Jun 2023Serotonin effects on cardiac hypertrophy, senescence, and failure are dependent either on activation of specific receptors or serotonin uptake and serotonin degradation...
Serotonin effects on cardiac hypertrophy, senescence, and failure are dependent either on activation of specific receptors or serotonin uptake and serotonin degradation by monoamine oxidases (MAOs). Receptor-dependent effects are specific for serotonin, but MAO-dependent effects are nonspecific as MAOs also metabolize other substrates such as catecholamines. Our study evaluates the role of MAO-A in serotonin- and norepinephrine-dependent cell damage. Experiments were performed in vivo to study the regulation of and expression and in vitro on isolated cultured adult rat ventricular cardiomyocytes (cultured for 24 h) to study the function of MAO-A. but not expression increased in maladaptive hypertrophic stages. Serotonin and norepinephrine induced morphologic cell damage (loss of rod-shaped cell structure). However, MAO-A inhibition suppressed serotonin-dependent but not norepinephrine-dependent damages. Serotonin but not norepinephrine caused a reduction in cell shortening in nondamaged cells. Serotonin induced mitochondria-dependent oxidative stress. In vivo, was induced during aging and hypertension but the expression of the corresponding serotonin uptake receptor () was reduced and enzymes that reduce either oxidative stress () or accumulation of 5-hydroxyindolacetaldehyde () were induced. In summary, the data show that MAO-A potentially affects cardiomyocytes' function but that serotonin is not necessarily the native substrate.
Topics: Rats; Animals; Myocytes, Cardiac; Serotonin; Norepinephrine; Monoamine Oxidase; Cardiomegaly
PubMed: 37371593
DOI: 10.3390/biom13061013 -
American Journal of Physiology.... Oct 2014
Ca2+ and cAMP signaling pathways interact to increase the diuretic effect of serotonin in Malpighian tubules of the kissing bug. Focus on "Serotonin triggers cAMP- and PKA-1-mediated intracellular calcium waves in Malpighian tubules of Rhodnius prolixus".
Topics: 8-Bromo Cyclic Adenosine Monophosphate; Animals; Calcium; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Ion Transport; Malpighian Tubules; Serotonin
PubMed: 25275012
DOI: 10.1152/ajpregu.00336.2014 -
ACS Chemical Neuroscience May 2017Although serotonin neurotransmission has been implicated in several neurodevelopmental and psychological disorders, the factors that drive dysfunction of the serotonin...
Although serotonin neurotransmission has been implicated in several neurodevelopmental and psychological disorders, the factors that drive dysfunction of the serotonin system are poorly understood. Current research regarding the serotonin system revolves around its dysfunction in neuropsychiatric disorders, but there is no database collating genetic mutations that result in serotonin abnormalities. To bridge this gap, we developed a list of genes in mice that, when perturbed, result in altered levels of serotonin either in brain or blood. Due to the intrinsic limitations of search, the current list should be considered a preliminary subset of all relevant cases. Nevertheless, it offered an opportunity to gain insight into what types of genes have the potential to impact serotonin by using gene ontology (GO). This analysis found that genes associated with monoamine metabolism were more often associated with increases in brain serotonin than decreases. Speculatively, this could be because several pathways (and therefore many genes) are responsible for the clearance and metabolism of serotonin whereas only one pathway (and therefore fewer genes) is directly involved in the synthesis of serotonin. Another contributor could be cross talk between monoamine systems such as dopamine. In contrast, genes that were associated with decreases in brain serotonin were more likely linked to a developmental process. Sensitivity of serotonin neurons to developmental perturbations could be due to their complicated neuroanatomy or possibly they may be negatively regulated by dysfunction of their innervation targets. Thus, these observations suggest hypotheses regarding the mechanisms underlying the vulnerability of brain serotonin neurotransmission.
Topics: Animals; Brain; Gene Expression; Mice; Mutation; Neurons; Serotonin
PubMed: 28418237
DOI: 10.1021/acschemneuro.6b00441 -
International Journal of Molecular... Jan 2020Adipocytes are dynamic cells that have critical functions to maintain body energy homeostasis. Adipocyte physiology is affected by the adipogenic differentiation, cell...
Adipocytes are dynamic cells that have critical functions to maintain body energy homeostasis. Adipocyte physiology is affected by the adipogenic differentiation, cell program, as well as by the exogenous stimulation of biochemical factors, such as serotonin and TNF-α. In this work, we investigated the global transcriptome modifications when porcine intramuscular preadipocyte (PIP) was differentiated into porcine mature adipocyte (pMA). Moreover, we studied transcriptome changes in pMA after stimulation with serotonin or TNF-α by using a microarray approach. Transcriptome analysis revealed that the expression of 270, 261, and 249 genes were modified after differentiation, or after serotonin and TNF-α stimulation, respectively. Expression changes in , , , , , , , , , , , , , , , , , , and genes which are enriched in the 'PPAR signaling' and 'insulin resistance' pathways were found in adipocytes during the differentiation process. Dose-dependent serotonin stimulation resulted in a decreased fat accumulation in pMAs. Serotonin-induced differentially expressed genes in pMAs were found to be involved in the significant enrichment of 'GPCR ligand-binding', 'cell chemotaxis', 'blood coagulation and complement', 'metabolism of lipid and lipoproteins', 'regulation of lipid metabolism by , and 'lipid digestion, mobilization and transport' pathways. TNF-α stimulation also resulted in transcriptome modifications linked with proinflammatory responses in the pMA of intramuscular origin. Our results provide a landscape of transcriptome modifications and their linked-biological pathways in response to adipogenesis, and exogenous stimulation of serotonin- and TNF-α to the pMA of intramuscular origin.
Topics: Adipocytes; Animals; Cell Differentiation; Cells, Cultured; Dose-Response Relationship, Drug; Female; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Lipid Metabolism; Muscle, Skeletal; Serotonin; Swine; Tumor Necrosis Factor-alpha
PubMed: 31963662
DOI: 10.3390/ijms21020638 -
Analytical Chemistry Jan 2020Although N-shaped fast scan cyclic voltammetry (N-FSCV) is well-established as an electroanalytical method to measure extracellular serotonin concentrations , it is in...
Although N-shaped fast scan cyclic voltammetry (N-FSCV) is well-established as an electroanalytical method to measure extracellular serotonin concentrations , it is in need of improvement in both sensitivity and selectivity. Based on our previous studies using fast cyclic square-wave voltammetry (FCSWV) for dopamine measurements, we have modified this technique to optimize the detection of serotonin . A series of large amplitude square-shaped potentials was superimposed onto an N-shaped waveform to provide cycling through multiple redox reactions within the N-shaped waveform to enhance the sensitivity and selectivity to serotonin measurement when combined with a two-dimensional voltammogram. N-Shaped fast cyclic square-wave voltammetry (N-FCSWV) showed significantly higher sensitivity to serotonin compared to conventional N-FSCV. In addition, N-FCSWV showed better performance than conventional N-shaped FSCV in differentiating serotonin from its major interferents, dopamine and 5-hydroxyindoleascetic acid (5-HIAA). It was also confirmed that the large amplitude of the square waveform did not influence local neuronal activity, and it could monitor electrical stimulation evoked phasic release of serotonin in the rat substantia nigra pars reticulata (SNr) before and after systemic injection of escitalopram (ESCIT, 10 mg/kg i.p.), a serotonin selective reuptake inhibitor.
Topics: Animals; Brain Chemistry; Electrochemical Techniques; Equipment Design; Male; Microelectrodes; Rats, Sprague-Dawley; Serotonin
PubMed: 31789495
DOI: 10.1021/acs.analchem.9b03164 -
Molecules (Basel, Switzerland) Mar 2021Intestinal enteroendocrine cells (EECs) respond to fatty acids from dietary and microbial origin by releasing neurotransmitters and hormones with various paracrine and... (Review)
Review
Intestinal enteroendocrine cells (EECs) respond to fatty acids from dietary and microbial origin by releasing neurotransmitters and hormones with various paracrine and endocrine functions. Much has become known about the underlying signaling mechanisms, including the involvement of G-protein coupled receptors (GPCRs), like free fatty acids receptors (FFARs). This review focusses on two more recently emerging research lines: the roles of odorant receptors (ORs), and those of fatty acid conjugates in gut. Odorant receptors belong to a large family of GPCRs with functional roles that only lately have shown to reach beyond the nasal-oral cavity. In the intestinal tract, ORs are expressed on serotonin (5-HT) and glucagon-like-peptide-1 (GLP-1) producing enterochromaffin and enteroendocrine L cells, respectively. There, they appear to function as chemosensors of microbiologically produced short-, and branched-chain fatty acids. Another mechanism of fatty acid signaling in the intestine occurs via their conjugates. Among them, conjugates of unsaturated long chain fatty acids and acetate with 5-HT, -acyl serotonins have recently emerged as mediators with immune-modulatory effects. In this review, novel findings in mechanisms and molecular players involved in intestinal fatty acid biology are highlighted and their potential relevance for EEC-mediated signaling to the pancreas, immune system, and brain is discussed.
Topics: Animals; Diet; Enteroendocrine Cells; Ethanolamine; Fatty Acids; Gastrointestinal Microbiome; Humans; Immunologic Factors; Intestines; Lipid Metabolism; Oleic Acids; Receptors, Odorant; Serotonin; Signal Transduction
PubMed: 33807994
DOI: 10.3390/molecules26051416 -
Biochimica Et Biophysica Acta Apr 2016Neurodegenerative disorders represent the culmination of numerous insults including oxidative stress. The long etiology of most of these disorders suggests that...
Neurodegenerative disorders represent the culmination of numerous insults including oxidative stress. The long etiology of most of these disorders suggests that lessening the effects of one or more of the insults could significantly delay disease onset. Antioxidants have been tested as possible therapeutics for neurodegenerative disorders, but with little success. Here we report that serotonin acts as a scavenger of hypochlorous acid (HOCl) in the brain. Serotonin was shown to prevent the oxidation of 2-thio-5-nitrobenzoate by HOCl in a biphasic manner. The first phase was a partial scavenging that occurred at concentrations of serotonin that exceeded those of HOCl. (1)H-NMR studies indicated that HOCl chlorinates both the aryl and akyl nitrogen atoms of serotonin. Thus, the oxidation of 2-thio-5-nitrobenzoate that occurred during the first phase of scavenging is likely due to the formation of serotonergic chloramines. A second phase of scavenging occurred at concentrations of HOCl that exceeded those of serotonin. Under these conditions, the chlorinated serotonin polymerized and formed inert aggregates. Serotonin was further shown to prevent the loss of cells and cellular α-ketoglutarate dehydrogenase complex activity caused by HOCl. Extracellular concentrations of serotonin in the brain can be elevated with selective serotonin reuptake inhibitors and suggests that such compounds could be used to increase the cerebral antioxidant capacity. Acute administration of selective serotonin reuptake inhibitors to mice treated with endotoxin partially mitigated sickness behavior and protein chlorination in the brain. These observations suggest that serotonin may act to suppress chlorinative stress in the brain.
Topics: Animals; Brain; Free Radical Scavengers; Halogenation; Humans; Hypochlorous Acid; Ketoglutarate Dehydrogenase Complex; Male; Mice; Oxidative Stress; Serotonin; THP-1 Cells
PubMed: 26699077
DOI: 10.1016/j.bbadis.2015.12.012 -
European Journal of Nuclear Medicine... Mar 2011The serotonergic system of the brain is complex, with an extensive innervation pattern covering all brain regions and endowed with at least 15 different receptors (each... (Review)
Review
The serotonergic system of the brain is complex, with an extensive innervation pattern covering all brain regions and endowed with at least 15 different receptors (each with their particular distribution patterns), specific reuptake mechanisms and synthetic processes. Many aspects of the functioning of the serotonergic system are still unclear, partially because of the difficulty of measuring physiological processes in the living brain. In this review we give an overview of the conventional methods of measuring serotonin synthesis and methods using positron emission tomography (PET) tracers, more specifically with respect to serotonergic function in affective disorders. Conventional methods are invasive and do not directly measure synthesis rates. Although they may give insight into turnover rates, a more direct measurement may be preferred. PET is a noninvasive technique which can trace metabolic processes, like serotonin synthesis. Tracers developed for this purpose are α-[(11)C]methyltryptophan ([(11)C]AMT) and 5-hydroxy-L-[β-(11)C]tryptophan ([(11)C]5-HTP). Both tracers have advantages and disadvantages. [(11)C]AMT can enter the kynurenine pathway under inflammatory conditions (and thus provide a false signal), but this tracer has been used in many studies leading to novel insights regarding antidepressant action. [(11)C]5-HTP is difficult to produce, but trapping of this compound may better represent serotonin synthesis. AMT and 5-HTP kinetics are differently affected by tryptophan depletion and changes of mood. This may indicate that both tracers are associated with different enzymatic processes. In conclusion, PET with radiolabelled substrates for the serotonergic pathway is the only direct way to detect changes of serotonin synthesis in the living brain.
Topics: Animals; Blood Platelets; Humans; Positron-Emission Tomography; Radioactive Tracers; Radiopharmaceuticals; Serotonin
PubMed: 21113591
DOI: 10.1007/s00259-010-1663-2 -
Biosensors & Bioelectronics Jul 2024Psychiatric disorders are associated with serve disturbances in cognition, emotional control, and/or behavior regulation, yet few routine clinical tools are available... (Review)
Review
Psychiatric disorders are associated with serve disturbances in cognition, emotional control, and/or behavior regulation, yet few routine clinical tools are available for the real-time evaluation and early-stage diagnosis of mental health. Abnormal levels of relevant biomarkers may imply biological, neurological, and developmental dysfunctions of psychiatric patients. Exploring biosensors that can provide rapid, in-situ, and real-time monitoring of psychiatric biomarkers is therefore vital for prevention, diagnosis, treatment, and prognosis of mental disorders. Recently, psychiatric biosensors with high sensitivity, selectivity, and reproducibility have been widely developed, which are mainly based on electrochemical and optical sensing technologies. This review presented psychiatric disorders with high morbidity, disability, and mortality, followed by describing pathophysiology in a biomarker-implying manner. The latest biosensors developed for the detection of representative psychiatric biomarkers (e.g., cortisol, dopamine, and serotonin) were comprehensively summarized and compared in their sensitivities, sensing technologies, applicable biological platforms, and integrative readouts. These well-developed biosensors are promising for facilitating the clinical utility and commercialization of point-of-care diagnostics. It is anticipated that mental healthcare could be gradually improved in multiple perspectives, ranging from innovations in psychiatric biosensors in terms of biometric elements, transducing principles, and flexible readouts, to the construction of 'Big-Data' networks utilized for sharing intractable psychiatric indicators and cases.
Topics: Humans; Biomarkers; Biosensing Techniques; Dopamine; Electrochemical Techniques; Mental Disorders; Mental Health; Serotonin
PubMed: 38631133
DOI: 10.1016/j.bios.2024.116242 -
Journal of Morphology May 2018Acoel worms are simple, often microscopic animals with direct development, a multiciliated epidermis, a statocyst, and a digestive parenchyma instead of a gut...
Acoel worms are simple, often microscopic animals with direct development, a multiciliated epidermis, a statocyst, and a digestive parenchyma instead of a gut epithelium. Morphological characters of acoels have been notoriously difficult to interpret due to their relative scarcity. The nervous system is one of the most accessible and widely used comparative features in acoels, which have a so-called commissural brain without capsule and several major longitudinal neurite bundles. Here, we use the selective binding properties of a neuropeptide antibody raised in echinoderms (SALMFamide2, or S2), and a commercial antibody against serotonin (5-HT) to provide additional characters of the acoel nervous system. We have prepared whole-mount immunofluorescent stainings of three acoel species: Symsagittifera psammophila (Convolutidae), Aphanostoma pisae, and the model acoel Isodiametra pulchra (both Isodiametridae). The commissural brain of all three acoels is delimited anteriorly by the ventral anterior commissure, and posteriorly by the dorsal posterior commissure. The dorsal anterior commissure is situated between the ventral anterior commissure and the dorsal posterior commissure, while the statocyst lies between dorsal anterior and dorsal posterior commissure. S2 and serotonin do not co-localise, and they follow similar patterns to each other within an animal. In particular, S2, but not 5-HT, stains a prominent commissure posterior to the main (dorsal) posterior commissure. We have for the first time observed a closed posterior loop of the main neurite bundles in S. psammophila for both the amidergic and the serotonergic nervous system. In I. pulchra, the lateral neurite bundles also form a posterior loop in our serotonergic nervous system stainings.
Topics: Animals; Invertebrates; Nervous System; Serotonin
PubMed: 29388261
DOI: 10.1002/jmor.20794