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Using immunocytochemistry, serotonergic nerve elements were documented in the nervous system of the planarian Girardia tigrina. Serotonin-immunopositive components were observed in the brain, ventral, dorsal and longitudinal nerve cords, transverse nerve commissures connecting the nerve cords, and in the nerve plexus. Whole-mount preparations of G. tigrina were analyzed by fluorescent and confocal laser scanning microscopy. An essential quantitative morphometric measurement of serotonin-immunopositive structures was conducted in three body regions (anterior, middle, and posterior) of the planarian. The number of serotonin neurons was maximal in the head region. The ventral nerve cords gradually decreased in thickness from anterior to posterior body ends. Physiological action of exogenously applied serotonin was studied in G. tigrina for the first time. It was found that serotonin (0.1 and 1 µmol L-1) accelerated eye regeneration. The transcriptome sequencing performed for the first time for the planarian G. tigrina revealed the transcripts of the tryptophan hydroxylase (trph), amino acid decarboxylase (aadc) and serotonin transporter (sert) genes. The data obtained indicate the presence of the components of serotonin pathway in G. tigrina. The identified transcripts can take part in serotonin turnover and participate in the realization of biological effects of serotonin in planarians, associated with eyes regeneration and differentiation.
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Planarias , Serotonina , Animales , Serotonina/metabolismo , Planarias/anatomía & histología , Planarias/fisiología , Triptófano Hidroxilasa/metabolismo , Triptófano Hidroxilasa/genética , Platelmintos , Neuronas Serotoninérgicas/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genéticaAsunto(s)
Memoria , Serotonina , Animales , Serotonina/metabolismo , Memoria/efectos de los fármacos , RatonesRESUMEN
An additional microscopic diagnostic sign has been identified for verification of asphyxial type of drowning. In white non-linear male rats (age 2 months) subjected to free drowning, significant hyperplasia of argyrophilic and morphofunctional activity of serotonin-containing APUD-cells of the laryngeal mucosa were revealed under conditions of acute anoxia in comparison with the intact control. These changes promote the development of laryngospasm, which prevents water penetration into the airways and lungs in asphyxial type of drowning. The presence of statistically significant hyperplasia of argyrophilic and morphofunctional activity of serotonin-containing APUD-cells of the laryngeal mucosa under conditions of acute anoxia can be used as an additional diagnostic criterion for asphyxial type of drowning in experimental studies.
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Asfixia , Ahogamiento , Serotonina , Animales , Ratas , Masculino , Ahogamiento/patología , Asfixia/patología , Serotonina/metabolismo , Laringe/patología , Agua Dulce , Mucosa Laríngea/patología , Laringismo/patologíaRESUMEN
Slow transit constipation (STC) is a long-lasting and prevalent intestinal condition, marked by hard, dry feces. The primary cause of STC may be attributed to an imbalance in the gut's microbial community and alterations in its metabolic byproducts. Tongbian formula (TB), a traditional Chinese medicinal formula, has been used to treat STC and shows a great effect on relieving constipation. The role of TB in regulating intestinal microbiota has not been fully elucidated. Herein, we investigated the potential effect of TB on gut microbiota and further explored the potential mechanism behind its effects. Our study demonstrated that TB significantly increased fecal water content and intestinal ink propulsion rate in loperamide (Lope)-induced STC rats. 5-HT signaling was suppressed in STC colon tissue, and the abundance of butyric acid (BA) in colonic contents was significantly down-regulated after Lope treatment. Notably, TB administration led to the restoration of microbial dysbiosis and the up-regulation of BA content, subsequently activating 5-HT signaling pathways. When BA was combined with a tryptophan hydroxylase-1 (TPH1) inhibitor, which is crucial for 5-HT synthesis, its therapeutic efficacy for treating STC was compromised. TB alleviates STC by reversing the intestinal microbiota imbalance and activating the 5-HT signaling in the colon through increasing BA levels. These findings suggest that TB is an ideal candidate for STC treatment.
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Ácido Butírico , Estreñimiento , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Serotonina , Transducción de Señal , Estreñimiento/tratamiento farmacológico , Estreñimiento/metabolismo , Animales , Ácido Butírico/farmacología , Transducción de Señal/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Ratas , Serotonina/metabolismo , Masculino , Ratas Sprague-Dawley , Tránsito Gastrointestinal/efectos de los fármacos , Loperamida , Modelos Animales de Enfermedad , Colon/metabolismo , Colon/efectos de los fármacosRESUMEN
A dual-template molecularly imprinted electrochemical sensor was developed for the simultaneous detection of serotonin (5-HT) and glutamate (Glu). First, amino-functionalized reduced graphene oxide (NRGO) was used as the modification material of a GCE to increase its electrical conductivity and specific surface area, using Glu and 5-HT as dual-template molecules and o-phenylenediamine (OPD) with self-polymerization ability as functional monomers. Through self-assembly and electropolymerization, dual-template molecularly imprinted polymers were formed on the electrode. After removing the templates, the specific recognition binding sites were exposed. The amount of NRGO, polymerization parameters, and elution parameters were further optimized to construct a dual-template molecularly imprinted electrochemical sensor, which can specifically recognize double-target molecules Glu and 5-HT. The differential pulse voltammetry (DPV) technique was used to achieve simultaneous detection of Glu and 5-HT based on their distinct electrochemical activities under specific conditions. The sensor showed a good linear relationship for Glu and 5-HT in the range 1 ~ 100 µM, and the detection limits were 0.067 µM and 0.047 µM (S/N = 3), respectively. The sensor has good reproducibility, repeatability, and selectivity. It was successfully utilized to simultaneously detect Glu and 5-HT in mouse serum, offering a more dependable foundation for objectively diagnosing and early warning of depression. Additionally, the double signal sensing strategy also provides a new approach for the simultaneous detection of both electroactive and non-electroactive substances.
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Técnicas Electroquímicas , Ácido Glutámico , Grafito , Límite de Detección , Impresión Molecular , Fenilendiaminas , Serotonina , Serotonina/sangre , Serotonina/análisis , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Animales , Ácido Glutámico/análisis , Ácido Glutámico/sangre , Ácido Glutámico/química , Grafito/química , Ratones , Fenilendiaminas/química , Depresión/diagnóstico , Depresión/sangre , Electrodos , Biomarcadores/sangre , Biomarcadores/análisis , Reproducibilidad de los ResultadosRESUMEN
The role of serotonin in human behaviour is informed by approaches which allow in vivo modification of synaptic serotonin. However, characterising the effects of increased serotonin signalling in human models of behaviour is challenging given the limitations of available experimental probes, notably selective serotonin reuptake inhibitors. Here we use a now-accessible approach to directly increase synaptic serotonin in humans (a selective serotonin releasing agent) and examine its influence on domains of behaviour historically considered core functions of serotonin. Computational techniques, including reinforcement learning and drift diffusion modelling, explain participant behaviour at baseline and after week-long intervention. Reinforcement learning models reveal that increasing synaptic serotonin reduces sensitivity for outcomes in aversive contexts. Furthermore, increasing synaptic serotonin enhances behavioural inhibition, and shifts bias towards impulse control during exposure to aversive emotional probes. These effects are seen in the context of overall improvements in memory for neutral verbal information. Our findings highlight the direct effects of increasing synaptic serotonin on human behaviour, underlining its role in guiding decision-making within aversive and more neutral contexts, and offering implications for longstanding theories of central serotonin function.
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Serotonina , Humanos , Serotonina/metabolismo , Masculino , Femenino , Adulto , Adulto Joven , Refuerzo en Psicología , Reacción de Prevención/efectos de los fármacos , Reacción de Prevención/fisiología , Emociones/fisiología , Inhibición Psicológica , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Aprendizaje/fisiología , Toma de Decisiones/fisiología , Memoria/fisiología , Memoria/efectos de los fármacosRESUMEN
Ketamine has been found to have rapid and potent antidepressant activity. However, despite the ubiquitous brain expression of its molecular target, the N-methyl-d-aspartate receptor (NMDAR), it was not clear whether there is a selective, primary site for ketamine's antidepressant action. We found that ketamine injection in depressive-like mice specifically blocks NMDARs in lateral habenular (LHb) neurons, but not in hippocampal pyramidal neurons. This regional specificity depended on the use-dependent nature of ketamine as a channel blocker, local neural activity, and the extrasynaptic reservoir pool size of NMDARs. Activating hippocampal or inactivating LHb neurons swapped their ketamine sensitivity. Conditional knockout of NMDARs in the LHb occluded ketamine's antidepressant effects and blocked the systemic ketamine-induced elevation of serotonin and brain-derived neurotrophic factor in the hippocampus. This distinction of the primary versus secondary brain target(s) of ketamine should help with the design of more precise and efficient antidepressant treatments.
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Antidepresivos , Depresión , Habénula , Ketamina , Receptores de N-Metil-D-Aspartato , Animales , Masculino , Ratones , Antidepresivos/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Depresión/tratamiento farmacológico , Depresión/metabolismo , Habénula/efectos de los fármacos , Habénula/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Ketamina/farmacología , Ketamina/administración & dosificación , Ratones Endogámicos C57BL , Ratones Noqueados , Células Piramidales/efectos de los fármacos , Células Piramidales/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/genética , Serotonina/metabolismoRESUMEN
Type 2 diabetes and depression co-occur in a bidirectional manner. Curcumin supplements exhibit antidepressant effects that may mitigate depression by modulating neurotransmitters and reducing inflammatory and oxidative stress pathways. This study aimed to evaluate the efficacy of curcumin in improving depression severity in obese type 2 diabetes patients. The study employed a randomized, double-blind, placebo-controlled trial design with 227 participants. The primary end-point was depression severity assessed using the Patient Health Questionnaire-9. Biomarkers were measured at baseline and at 3-, 6-, 9-, and 12-month intervals. The biomarkers assessed were serotonin levels, pro-inflammatory cytokines (interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha), antioxidant activities (total antioxidant status, glutathione peroxidase, and superoxide dismutase), and malondialdehyde. After 12 months, the curcumin group exhibited significantly improved depression severity (p = 0.000001). The curcumin group had higher levels of serotonin (p < 0.0001) but lower levels of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha (p < 0.001 for all) than the placebo group. Total antioxidant status, glutathione peroxidase activity, and superoxide dismutase activity were elevated in the curcumin group, whereas malondialdehyde levels were greater in the placebo group (p < 0.001 for all). These findings suggest curcumin may have antidepressant effects on obese type 2 diabetes patients.
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Antioxidantes , Biomarcadores , Curcumina , Depresión , Diabetes Mellitus Tipo 2 , Obesidad , Humanos , Curcumina/farmacología , Curcumina/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Masculino , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Método Doble Ciego , Femenino , Persona de Mediana Edad , Depresión/tratamiento farmacológico , Depresión/etiología , Biomarcadores/sangre , Malondialdehído/sangre , Estrés Oxidativo/efectos de los fármacos , Serotonina/metabolismo , Serotonina/sangre , Antidepresivos/uso terapéutico , Antidepresivos/farmacología , Adulto , Glutatión Peroxidasa/sangre , Glutatión Peroxidasa/metabolismo , Superóxido Dismutasa/sangre , Superóxido Dismutasa/metabolismo , Citocinas/sangreRESUMEN
Methylphenidate (MPD) remains a cornerstone pharmacological intervention for managing ADHD, yet its increasing usage among ordinary youth and adults outside clinical contexts necessitates a thorough investigation into its developmental effects. This study seeks to simultaneously investigate the behavioral and neuronal changes within the dorsal raphe (DR) nucleus, a center of serotonergic neurons in the mammalian brain, before and after the administration of varying doses of acute and chronic MPD in freely behaving young and adult rats implanted with DR recording electrodes. Wireless neuronal and behavioral recording systems were used over 10 consecutive experimental days. Eight groups were examined: saline, 0.6, 2.5, and 10.0 mg/kg MPD for both young and adult rats. Six daily MPD injections were administered on experimental days 1 to 6, followed by a three-day washout period and MPD re-administration on experimental day 10 (ED10). The analysis of neuronal activity recorded from 504 DR neurons (DRNs) in young rats and 356 DRNs in adult rats reveals significant age-dependent differences in acute and chronic MPD responses. This study emphasizes the importance of aligning electrophysiological evaluations with behavioral outcomes following extended MPD exposure, elucidating the critical role of DRNs and serotonin signaling in modulating MPD responses and delineating age-specific variations in young versus adult rat models.
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Conducta Animal , Núcleo Dorsal del Rafe , Metilfenidato , Serotonina , Animales , Metilfenidato/farmacología , Núcleo Dorsal del Rafe/efectos de los fármacos , Núcleo Dorsal del Rafe/metabolismo , Ratas , Serotonina/metabolismo , Masculino , Conducta Animal/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas Serotoninérgicas/efectos de los fármacos , Neuronas Serotoninérgicas/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Factores de EdadRESUMEN
Copper is a trace element whose electronic configuration provides it with essential structural and catalytic functions. However, in excess, both its high protein affinity and redox-catalyzing properties can lead to hazardous consequences. In addition to promoting oxidative stress, copper is gaining interest for its effects on neurotransmission through modulation of GABAergic and glutamatergic receptors and interaction with the dopamine reuptake transporter. The aim of the present study was to investigate the effects of copper overexposure on the levels of dopamine, noradrenaline, and serotonin, or their main metabolites in rat's striatum extracellular fluid. Copper was injected intraperitoneally using our previously developed model, which ensured striatal overconcentration (2 mg CuCl2/kg for 30 days). Subsequently, extracellular fluid was collected by microdialysis on days 0, 15, and 30. Dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and noradrenaline (NA) levels were then determined by HPLC coupled with electrochemical detection. We observed a significant increase in the basal levels of DA and HVA after 15 days of treatment (310% and 351%), which was maintained after 30 days (358% and 402%), with no significant changes in the concentrations of 5-HIAA, DOPAC, and NA. Copper overload led to a marked increase in synaptic DA concentration, which could contribute to the psychoneurological alterations and the increased oxidative toxicity observed in Wilson's disease and other copper dysregulation states.
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Cobre , Cuerpo Estriado , Dopamina , Líquido Extracelular , Ácido Homovanílico , Animales , Dopamina/metabolismo , Cobre/metabolismo , Ácido Homovanílico/metabolismo , Ratas , Masculino , Líquido Extracelular/metabolismo , Cuerpo Estriado/metabolismo , Ácido 3,4-Dihidroxifenilacético/metabolismo , Ratas Wistar , Serotonina/metabolismo , Norepinefrina/metabolismoRESUMEN
Exposure to industrial contaminants has been implicated in neurobehavioral toxicity in humans. To explore this potential risk, we investigated the neurotoxic effects of oral exposure to a complex groundwater mixture containing petroleum hydrocarbons, pesticides, heavy metals, and unknown parent and breakdown products using male and female Sprague Dawley rats. Rats were randomly divided into six groups and orally exposed daily via drinking water to: (i) tap water, (ii) 10â¯% v/v low impact groundwater, and (iii) 0.01â¯%, 0.1â¯%, 1â¯%, and 10â¯% high-impact groundwater for 60 days. Medium- and long-term memory (measured using the novel object recognition task) were impaired. However, no gross motor or coordination deficits were observed by the end of the study period (rotarod test). Doppler ultrasound of the middle cerebral and common carotid arteries was performed to examine the hemodynamic changes. The common carotid blood flow decreased in the groundwater-exposed rats compared to that in the control. However, no significant differences in cerebral blood velocity were observed between the exposed and control groups. A significant reduction in hippocampal serotonin levels was observed in groundwater-exposed rats relative to that in the control group. Collectively, these results indicate that impaired recognition memory in rats exposed to groundwater is accompanied by reduced cranial blood flow and hippocampal neurotoxicity, characterized by altered serotonergic signalling. The levels of detected contaminants known to cause neural or vascular damage were of magnitudes lower than the concentrations of contaminants found in the groundwater mixture, meaning the culprit chemical identity remains unknown. This study emphasizes the need to use whole mixture in exposures when dealing with complex contaminated sites rather than the use of individual compounds.
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Circulación Cerebrovascular , Agua Subterránea , Hipocampo , Trastornos de la Memoria , Ratas Sprague-Dawley , Contaminantes Químicos del Agua , Animales , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Agua Subterránea/química , Masculino , Femenino , Contaminantes Químicos del Agua/toxicidad , Ratas , Trastornos de la Memoria/inducido químicamente , Circulación Cerebrovascular/efectos de los fármacos , Serotonina/metabolismo , Síndromes de Neurotoxicidad/fisiopatología , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/patología , Reconocimiento en Psicología/efectos de los fármacosRESUMEN
Fast-scan cyclic voltammetry (FSCV) is an electrochemical sensing technique that can be used for neurochemical sensing with high spatiotemporal resolution. Carbon fiber microelectrodes (CFMEs) are traditionally used as FSCV sensors. However, CFMEs are prone to electrochemical fouling caused by oxidative byproducts of repeated serotonin (5-HT) exposure, which makes them less suitable as chronic 5-HT sensors. Our team is developing a boron-doped diamond microelectrode (BDDME) that has previously been shown to be relatively resistant to fouling caused by protein adsorption (biofouling). We sought to determine if this BDDME exhibits resistance to electrochemical fouling, which we explored on electrodes fabricated with either femtosecond laser cutting or physical cleaving. We recorded the oxidation current response after 25 repeated injections of 5-HT in a flow-injection cell and compared the current drop from the first with the last injection. The 5-HT responses were compared with dopamine (DA), a neurochemical that is known to produce minimal fouling oxidative byproducts and has a stable repeated response. Physical cleaving of the BDDME yielded a reduction in fouling due to 5-HT compared with the CFME and the femtosecond laser cut BDDME. However, the femtosecond laser cut BDDME exhibited a large increase in sensitivity over the cleaved BDDME. An extended stability analysis was conducted for all device types following 5-HT fouling tests. This analysis demonstrated an improvement in the long-term stability of boron-doped diamond over CFMEs, as well as a diminishing sensitivity of the laser-cut BDDME over time. This work reports the electrochemical fouling performance of the BDDME when it is repeatedly exposed to DA or 5-HT, which informs the development of a chronic, diamond-based electrochemical sensor for long-term neurotransmitter measurements in vivo.
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Boro , Diamante , Técnicas Electroquímicas , Microelectrodos , Serotonina , Serotonina/análisis , Boro/química , Diamante/química , Técnicas Biosensibles , Dopamina/análisis , Fibra de Carbono , Oxidación-ReducciónRESUMEN
Dietary components, including dietary fiber, unsaturated fatty acids, and polyphenols, along with meal timing and spacing, significantly affect the microbiota's capacity to produce various metabolites essential for quality sleep and overall health. This review explores the role of gut microbiota in regulating sleep through various metabolites such as short-chain fatty acids, tryptophan, serotonin, melatonin, and gamma-aminobutyric acid. A balanced diet rich in plant-based foods enhances the production of these sleep-regulating metabolites, potentially benefiting overall health. This review aims to investigate how dietary habits affect gut microbiota composition, the metabolites it produces, and the subsequent impact on sleep quality and related health conditions.
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Dieta , Microbioma Gastrointestinal , Calidad del Sueño , Microbioma Gastrointestinal/fisiología , Humanos , Fibras de la Dieta/administración & dosificación , Melatonina , Conducta Alimentaria/fisiología , Polifenoles , Sueño/fisiología , Ácidos Grasos Volátiles/metabolismo , Serotonina/metabolismoRESUMEN
PURPOSE: For understanding the neurochemical mechanism of neuropsychiatric conditions associated with cognitive deficits it is of major relevance to elucidate the influence of serotonin (5-HT) agonists and antagonists on memory function as well dopamine (DA) and 5-HT release and metabolism. In the present study, we assessed the effects of the 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) and the 5-HT2A receptor altanserin (ALT) on object and place recognition memory and cerebral neurotransmitters and metabolites in the rat. METHODS: Rats underwent a 5-min exploration trial in an open field with two identical objects. After systemic injection of a single dose of either DOI (0.1 mg/kg), ALT (1 mg/kg) or the respectice vehicle (0.9 % NaCl, 50 % DMSO), rats underwent a 5-min test trial with one of the objects replaced by a novel one and the other object transferred to a novel place. Upon the assessment of object exploration and motor/exploratory behaviors, rats were sacrificed. DA, 5-HT and metabolite levels were analyzed in cingulate (CING), caudateputamen (CP), nucleus accumbens (NAC), thalamus (THAL), dorsal (dHIPP) and ventral hippocampus (vHIPP), brainstem and cerebellum with high performance liquid chromatography. RESULTS: DOI decreased rearing but increased head-shoulder motility relative to vehicle. Memory for object and place after both DOI and ALT was not different from vehicle. Network analyses indicated that DOI inhibited DA metabolization in CING, CP, NAC, and THAL, but facilitated it in dHIPP. Likewise, DOI inhibited 5-HT metabolization in CING, NAC, and THAL. ALT facilitated DA metabolization in the CING, NAC, dHIPP, vHIPP, and CER, but inhibited it in the THAL. Additionally, ALT facilitated 5-HT metabolization in NAC and dHIPP. CONCLUSIONS: DOI and ALT differentially altered the quantitative relations between the neurotransmitter/metabolite levels in the individual brain regions, by inducing region-specific shifts in the metabolization pathways. Findings are relevant for understanding the neurochemistry underlying DAergic and/or 5-HTergic dysfunction in neurological and psychiatric conditions.
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Anfetaminas , Encéfalo , Dopamina , Serotonina , Animales , Ratas , Serotonina/metabolismo , Masculino , Dopamina/metabolismo , Anfetaminas/farmacología , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Ketanserina/farmacología , Ketanserina/análogos & derivados , Agonistas del Receptor de Serotonina 5-HT2/farmacología , Ratas WistarRESUMEN
Liraglutide, a glucagon-like peptide 1 analog used to treat type 2 diabetes and obesity, is a potential new treatment modality for bile acid (BA) diarrhea. Here, we show that administration of liraglutide significantly decreased total BAs, especially the primary BAs, including cholic acid, chenodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, glycocholic acid, and ß-muricholic acid, in the liver and feces. In addition, liraglutide significantly decreased tryptophan metabolites, including L-tryptophan, serotonin, 5-hydroxy indole-3-acetic acid, L-kynurenine, and xanthurenic acid, in the colon, whereas it significantly increased indole-3-propionic acid. Moreover, the administration of liraglutide remarkably decreased the expression of apical sodium-dependent bile acid transporter, which mediates BA uptake across the apical brush border member in the ileum, ileal BA binding protein, and fibroblast growth factor 15 in association with decreased expression of the BA-activated nuclear receptor farnesoid X receptor and the heteromeric organic solute transporter Ostα/ß, which induces BA excretion, in the ileum. Liraglutide acutely decreased body weight and blood glucose levels in association with decreases in plasma insulin and serotonin levels in food-deprived mice. These findings suggest the potential of liraglutide as a novel inhibitor of primary BAs and serotonin in the colon.
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Ácidos y Sales Biliares , Colon , Receptor del Péptido 1 Similar al Glucagón , Liraglutida , Serotonina , Animales , Liraglutida/farmacología , Serotonina/metabolismo , Ácidos y Sales Biliares/metabolismo , Ratones , Colon/metabolismo , Colon/efectos de los fármacos , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/agonistas , Masculino , Transportadores de Anión Orgánico Sodio-Dependiente/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores Citoplasmáticos y Nucleares/agonistas , Triptófano/metabolismo , Triptófano/farmacología , Triptófano/análogos & derivados , Ratones Endogámicos C57BL , Íleon/metabolismo , Íleon/efectos de los fármacos , Hígado/metabolismo , Hígado/efectos de los fármacos , Ácidos Cólicos , Proteínas de Transporte de Membrana , SimportadoresRESUMEN
The resurgence of interest in psychedelics as treatments for psychiatric disorders necessitates a better understanding of potential sex differences in response to these substances. Sex as a biological variable (SABV) has been historically neglected in medical research, posing limits to our understanding of treatment efficacy. Human studies have provided insights into the efficacy of psychedelics across various diagnoses and aspects of cognition, yet sex-specific effects remain unclear, making it difficult to draw strong conclusions about sex-dependent differences in response to psychedelic treatments. Compounding this further, animal studies used to understand biological mechanisms of psychedelics predominantly use one sex and present mixed neurobiological and behavioral outcomes. Studies that do include both sexes often do not investigate sex differences further, which may hinder the translation of findings to the clinic. In reviewing sex differences in responses to psychedelics, we will highlight the direct interaction between estrogen (the most extensively studied steroid hormone) and the serotonin system (central to the mechanism of action of psychedelics), and the potential that estrogen-serotonin interactions may influence the efficacy of psychedelics in female participants. Estrogen influences serotonin neurotransmission by affecting its synthesis and release, as well as modulating the sensitivity and responsiveness of serotonin receptor subtypes in the brain. This could potentially influence the efficacy of psychedelics in females by modifying their therapeutic efficacy across menstrual cycles and developmental stages. Investigating this interaction in the context of psychedelic research could aid in the advancement of therapeutic outcomes, especially for conditions with sex-specific prevalence.
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Alucinógenos , Serotonina , Caracteres Sexuales , Alucinógenos/farmacología , Humanos , Femenino , Animales , Masculino , Serotonina/metabolismo , Estrógenos/farmacologíaRESUMEN
Abdominal surgery such as ovariectomy is a traumatic event that can cause oxidative stress. The aim of the present study was to evaluate the concentration of serotonin in relation to ovariectomy-induced oxidative stress in dogs undergoing general anesthesia. Thirty-two female dogs, under general anesthesia, received meloxicam before surgery (0.2 mgkg-1 SC) and after surgery (0.1 mgkg-1 OS every 24 h). The physiological, hematological, and biochemical parameters: glycemia, aspartate transaminase (AST), alanine aminotransferase (ALT), total protein, albumin and BUN were evaluated. Oxidative stress was determined by malondialdehyde (MDA) assay, catalase (CAT), superoxide dismutase (SOD), myeloperoxidase (MPO) and butyrylcholinesterase (BuChe) at baseline, 36 and 48 h after the last administration of meloxicam. Serotonin (5-HT) concentration was also evaluated at baseline, 36 and 48 h after the last administration of meloxicam. Responses to surgical stimulus were evaluated. Physiological and hematological parameters they fell within the normal ranges for anesthetized dogs. Glycemia increased, albumin levels decreased after surgery. No rescue analgesia was required. MDA and 5-HT concentrations significantly increased from the baseline at 36 and 48 h after surgery (p < .001). 5-HT levels could be used as an indicator for oxidative stress induced by surgery and it might be employed for objectively quantifying the well-being of the surgical patient.
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Anestesia General , Meloxicam , Ovariectomía , Estrés Oxidativo , Serotonina , Animales , Perros , Femenino , Ovariectomía/veterinaria , Estrés Oxidativo/efectos de los fármacos , Anestesia General/veterinaria , Anestesia General/efectos adversos , Serotonina/sangre , Meloxicam/farmacología , Meloxicam/administración & dosificación , Malondialdehído/sangreRESUMEN
Neuroendocrine tumors are uncommon in the gastrointestinal system but can develop in the majority of the body's epithelial organs. Our goal was to examine the presence and clinical application of serum dopamine (DA), serotonin (ST), norepinephrine (NE), and epinephrine (EPI), in addition to determining the significance of the Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), and systemic inflammatory response (SIR) markers as a prognostic factor for patients with colorectal neuroendocrine tumors (CR-NETs), in various tumor-node-metastasis (TNM) stages. We also wanted to identify the possible connection between them. This study included 25 consecutive patients who were diagnosed with CR-NETs and a control group consisting of 60 patients with newly diagnosed colorectal cancer (CRC). We used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. This study revealed that CR-NET patients showed significantly higher serum levels of DA compared to CRC patients. We showed that serum DA was present in the early stages of CR-NETs, with increasing levels as we advanced through the TNM stages. Moreover, we found a close relationship between the levels of DA and the inflammation and nutritional status of the CR-NET patients in this study. CR-NET patients from the PNI < 47.00 subgroup had a higher level of DA than those from the PNI ≥ 47.00 subgroup. Pearson's correlation analysis revealed correlations between DA, PNI, and the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR). Both hematological indices were negatively correlated with albumin (ALB). Our investigation's findings relating to the PNI, GPS, SIR, and DA indicate that these tools can be markers of nutritional and systemic inflammatory status, are simple to use, and are repeatable. Further research on this topic could provide valuable insights into which biomarkers to incorporate into clinical practice for the management of CR-NET patients.
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Neoplasias Colorrectales , Dopamina , Epinefrina , Estadificación de Neoplasias , Tumores Neuroendocrinos , Norepinefrina , Serotonina , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/sangre , Femenino , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/sangre , Tumores Neuroendocrinos/diagnóstico , Serotonina/sangre , Epinefrina/sangre , Pronóstico , Norepinefrina/sangre , Anciano , Dopamina/sangre , Dopamina/metabolismo , Adulto , Biomarcadores de Tumor/sangre , Evaluación Nutricional , Neurotransmisores/sangre , Neurotransmisores/metabolismo , Inflamación/sangre , Inflamación/patologíaRESUMEN
BACKGROUND: Despite extensive studies on the neurobiological correlates of traumatic brain injury (TBI), little is known about its molecular determinants on long-term consequences, such as dementia and Alzheimer's disease (AD). METHODS: Here, we carried out behavioural studies and an extensive biomolecular analysis, including inflammatory cytokines, gene expression and the combination of LC-HRMS and MALDI-MS Imaging to elucidate the targeted metabolomics and lipidomics spatiotemporal alterations of brains from wild-type and APP-SWE mice, a genetic model of AD, at the presymptomatic stage, subjected to mild TBI. RESULTS: We found that brain injury does not affect cognitive performance in APP-SWE mice. However, we detected an increase of key hallmarks of AD, including Aß1-42 levels and BACE1 expression, in the cortices of traumatized transgenic mice. Moreover, significant changes in the expanded endocannabinoid (eCB) system, or endocannabinoidome (eCBome), occurred, including increased levels of the endocannabinoid 2-AG in APP-SWE mice in both the cortex and hippocampus, and N-acylserotonins, detected for the first time in the brain. The gene expression of enzymes for the biosynthesis and inactivation of eCBs and eCB-like mediators, and some of their main molecular targets, also underwent significant changes. We also identified the formation of heteromers between cannabinoid 1 (CB1) and serotonergic 2A (5HT2A) receptors, whose levels increased in the cortex of APP-SWE mTBI mice, possibly contributing to the exacerbated pathophysiology of AD induced by the trauma. CONCLUSIONS: Mild TBI induces biochemical changes in AD genetically predisposed mice and the eCBome may play a role in the pathogenetic link between brain injury and neurodegenerative disorders also by interacting with the serotonergic system.
Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Endocannabinoides , Ratones Transgénicos , Animales , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/genética , Ratones , Endocannabinoides/metabolismo , Disfunción Cognitiva/metabolismo , Serotonina/metabolismo , Biomarcadores/metabolismo , Masculino , Conmoción Encefálica/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Encéfalo/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Síntomas Prodrómicos , Péptidos beta-Amiloides/metabolismoRESUMEN
Carcinoid crisis (CC) has classically been considered the extreme end of the spectrum of carcinoid syndrome (CS). However, this presumption and other aspects of CC remain poorly understood. Consequently, current clinical guidelines are based on a low quality of evidence. There is no standard definition of CC and its incidence is unknown. Patients with florid CS and elevated serotonin (or its derivatives) which develop CC have been reported during decades. Nevertheless, the hypothesis that CC is due to the sudden massive release of serotonin or other vasoactive substances is unproven. Many triggers of CC (surgery, anaesthesia, peptide receptor radionuclide therapy, tumour biopsy or liver-directed treatments) have been proposed. However, data from studies are heterogeneous and even contradictory. Finally, the role of octreotide in the prevention of CC has been questioned. Herein, we report a clinical case and perform a critical review of the evidence available today on this topic.