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1.
Eur J Sport Sci ; 24(6): 721-731, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38874966

ABSTRACT

It has been assumed that exercise intensity variation throughout a cycling time trial (TT) occurs in alignment of various metabolic changes to prevent premature task failure. However, this assumption is based on target metabolite responses, which limits our understanding of the complex interconnection of metabolic responses during exercise. The current study characterized the metabolomic profile, an untargeted metabolic analysis, after specific phases of a cycling 4-km TT. Eleven male cyclists performed three separated TTs in a crossover counterbalanced design, which were interrupted at the end of the fast-start (FS, 600 ± 205 m), even-pace (EP, 3600 ± 190 m), or end-spurt (ES, 4000 m) phases. Blood samples were taken before any exercise and 5 min after exercise cessation, and the metabolomic profile characterization was performed using Nuclear Magnetic Resonance metabolomics. Power output (PO) was also continually recorded. There were higher PO values during the FS and ES compared to the EP (all p < 0.05), which were accompanied by distinct metabolomic profiles. FS showed high metabolite expression in TCA cycle and its related pathways (e.g., glutamate, citric acid, and valine metabolism); whereas, the EP elicited changes associated with antioxidant effects and oxygen delivery adjustment. Finally, ES was related to pathways involved in NAD turnover and serotonin metabolism. These findings suggest that the specific phases of a cycling TT are accompanied by distinct metabolomic profiles, providing novel insights regarding the relevance of specific metabolic pathways on the process of exercise intensity regulation.


Subject(s)
Bicycling , Cross-Over Studies , Metabolome , Humans , Male , Metabolome/physiology , Adult , Bicycling/physiology , Citric Acid Cycle , Serotonin/blood , NAD/blood , NAD/metabolism , Young Adult , Glutamic Acid/blood , Glutamic Acid/metabolism , Metabolomics , Valine/blood , Citric Acid/blood
2.
Int J Mol Sci ; 25(11)2024 May 24.
Article in English | MEDLINE | ID: mdl-38891901

ABSTRACT

The diverse effects of serotonin on cognition may emerge from the modulation of large-scale brain networks that support distinct cognitive processes. Yet, the specific effect of serotoninergic modulation on the properties of these networks remains elusive. Here, we used a simultaneous PET-fMRI scanner combined with graph theory analyses to investigate the modulation of network properties by the Serotonin Transporter (SERT) availability measured in the dorsal raphe nucleus (DRN). We defined global efficiency as the average mean of efficiencies over all pairs of distinct nodes of specific brain networks, and determined whether SERT levels correlated with the global efficiency of each network. SERT availability in the DRN correlated negatively with the global efficiency of the executive control brain network, which is engaged in cognitive control and directed attention. No relationship was observed between SERT availability and the global efficiency of the default mode or the salience brain networks. These findings indicate a specific role of serotoninergic modulation in the executive control brain network via a change in its global efficiency.


Subject(s)
Brain , Executive Function , Magnetic Resonance Imaging , Serotonin Plasma Membrane Transport Proteins , Serotonin Plasma Membrane Transport Proteins/metabolism , Humans , Male , Executive Function/physiology , Brain/metabolism , Brain/diagnostic imaging , Magnetic Resonance Imaging/methods , Adult , Nerve Net/metabolism , Nerve Net/physiology , Female , Positron-Emission Tomography/methods , Serotonin/metabolism , Young Adult , Dorsal Raphe Nucleus/metabolism , Brain Mapping
3.
Int J Mol Sci ; 25(11)2024 May 29.
Article in English | MEDLINE | ID: mdl-38892140

ABSTRACT

The study of the mechanisms by which melatonin protects against cadmium (Cd) toxicity in plants is still in its infancy, particularly at the molecular level. In this study, the gene encoding a novel serotonin N-acetyltransferase 3 (SNAT3) in rice, a pivotal enzyme in the melatonin biosynthetic pathway, was cloned. Rice (Oryza sativa) OsSNAT3 is the first identified plant ortholog of archaeon Thermoplasma volcanium SNAT. The purified recombinant OsSNAT3 catalyzed the conversion of serotonin and 5-methoxytryptamine to N-acetylserotonin and melatonin, respectively. The suppression of OsSNAT3 by RNAi led to a decline in endogenous melatonin levels followed by a reduction in Cd tolerance in transgenic RNAi rice lines. In addition, the expression levels of genes encoding the endoplasmic reticulum (ER) chaperones BiP3, BiP4, and BiP5 were much lower in RNAi lines than in the wild type. In transgenic rice plants overexpressing OsSNAT3 (SNAT3-OE), however, melatonin levels were higher than in wild-type plants. SNAT3-OE plants also tolerated Cd stress, as indicated by seedling growth, malondialdehyde, and chlorophyll levels. BiP4 expression was much higher in the SNAT3-OE lines than in the wild type. These results indicate that melatonin engineering could help crops withstand Cd stress, resulting in high yields in Cd-contaminated fields.


Subject(s)
Arylalkylamine N-Acetyltransferase , Cadmium , Gene Expression Regulation, Plant , Melatonin , Oryza , Plant Proteins , Plants, Genetically Modified , Stress, Physiological , Oryza/genetics , Oryza/metabolism , Oryza/drug effects , Melatonin/metabolism , Melatonin/pharmacology , Cadmium/metabolism , Cadmium/toxicity , Plant Proteins/metabolism , Plant Proteins/genetics , Plants, Genetically Modified/metabolism , Arylalkylamine N-Acetyltransferase/metabolism , Arylalkylamine N-Acetyltransferase/genetics , Molecular Chaperones/metabolism , Molecular Chaperones/genetics , Serotonin/metabolism
4.
Commun Biol ; 7(1): 710, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38851804

ABSTRACT

Selective serotonin reuptake inhibitors (SSRIs) are widely used for depression based on the monoamine deficiency hypothesis. However, the clinical use of these agents is controversial, in part because of their variable clinical efficacy and in part because of their delayed onset of action. Because of the complexities involved in replicating human disease and clinical dosing in animal models, the scientific community has not reached a consensus on the reasons for these phenomena. In this work, we create a theoretical hippocampal model incorporating escitalopram's pharmacokinetics, pharmacodynamics (competitive and non-competitive inhibition, and serotonin transporter (SERT) internalization), inflammation, and receptor dynamics. With this model, we simulate chronic oral escitalopram in mice showing that days to weeks are needed for serotonin levels to reach steady-state. We show escitalopram's chemical efficacy is diminished under inflammation. Our model thus offers mechanisms for how chronic escitalopram affects brain serotonin, emphasizing the importance of optimized dose and time for future antidepressant discoveries.


Subject(s)
Escitalopram , Inflammation , Selective Serotonin Reuptake Inhibitors , Serotonin Plasma Membrane Transport Proteins , Serotonin Plasma Membrane Transport Proteins/metabolism , Animals , Selective Serotonin Reuptake Inhibitors/pharmacology , Mice , Inflammation/drug therapy , Inflammation/metabolism , Escitalopram/pharmacology , Hippocampus/metabolism , Hippocampus/drug effects , Serotonin/metabolism , Humans , Citalopram/pharmacology
5.
Pak J Pharm Sci ; 37(2(Special)): 435-442, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38822547

ABSTRACT

Depression is a common non-motor symptom of Parkinson's disease. Previous studies demonstrated that hydroxysafflor yellow A had properties of improving motor symptoms of Parkinson's disease. The effect of hydroxysafflor yellow A on depression in Parkinson's disease mice is investigated in this study. To induce Parkinson's disease model, male Swiss mice were exposed to rotenone (30 mg/kg) for 6 weeks. The chronic unpredictable mild stress was employed to induce depression from week 3 to week 6. Sucrose preference, tail suspension, and forced swimming tests were conducted. Golgi and Nissl staining of hippocampus were carried out. The levels of dopamine, 5-hydroxytryptamine and the expression of postsynaptic density protein 95, brain-derived neurotrophic factor in hippocampus were assayed. It showed that HSYA improved the depression-like behaviors of Parkinson's disease mice. Hydroxysafflor yellow A attenuated the injury of nerve and elevated contents of dopamine, 5-hydroxytryptamine in hippocampus. Treatment with hydroxysafflor yellow A also augmented the expression of postsynaptic density protein 95 and brain-derived neurotrophic factor. These findings suggest that hydroxysafflor yellow A ameliorates depression-like behavior in Parkinson's disease mice through regulating the contents of postsynaptic density protein 95 and brain-derived neurotrophic factor, therefore protecting neurons and neuronal dendrites of the hippocampus.


Subject(s)
Behavior, Animal , Brain-Derived Neurotrophic Factor , Chalcone , Depression , Hippocampus , Quinones , Serotonin , Animals , Quinones/pharmacology , Quinones/therapeutic use , Chalcone/analogs & derivatives , Chalcone/pharmacology , Chalcone/therapeutic use , Male , Mice , Brain-Derived Neurotrophic Factor/metabolism , Depression/drug therapy , Depression/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/pathology , Behavior, Animal/drug effects , Serotonin/metabolism , Dopamine/metabolism , Rotenone/pharmacology , Disease Models, Animal , Disks Large Homolog 4 Protein/metabolism , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Parkinson Disease/psychology
6.
FASEB J ; 38(11): e23648, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38822661

ABSTRACT

Previous studies on germ-free (GF) animals have described altered anxiety-like and social behaviors together with dysregulations in brain serotonin (5-HT) metabolism. Alterations in circulating 5-HT levels and gut 5-HT metabolism have also been reported in GF mice. In this study, we conducted an integrative analysis of various behaviors as well as markers of 5-HT metabolism in the brain and along the GI tract of GF male mice compared with conventional (CV) ones. We found a strong decrease in locomotor activity, accompanied by some signs of increased anxiety-like behavior in GF mice compared with CV mice. Brain gene expression analysis showed no differences in HTR1A and TPH2 genes. In the gut, we found decreased TPH1 expression in the colon of GF mice, while it was increased in the cecum. HTR1A expression was dramatically decreased in the colon, while HTR4 expression was increased both in the cecum and colon of GF mice compared with CV mice. Finally, SLC6A4 expression was increased in the ileum and colon of GF mice compared with CV mice. Our results add to the evidence that the microbiota is involved in regulation of behavior, although heterogeneity among studies suggests a strong impact of genetic and environmental factors on this microbiota-mediated regulation. While no impact of GF status on brain 5-HT was observed, substantial differences in gut 5-HT metabolism were noted, with tissue-dependent results indicating a varying role of microbiota along the GI tract.


Subject(s)
Behavior, Animal , Germ-Free Life , Serotonin , Animals , Serotonin/metabolism , Mice , Male , Gastrointestinal Microbiome/physiology , Brain/metabolism , Tryptophan Hydroxylase/metabolism , Tryptophan Hydroxylase/genetics , Anxiety/metabolism , Anxiety/microbiology , Serotonin Plasma Membrane Transport Proteins/metabolism , Serotonin Plasma Membrane Transport Proteins/genetics , Mice, Inbred C57BL , Receptor, Serotonin, 5-HT1A/metabolism , Receptor, Serotonin, 5-HT1A/genetics , Colon/metabolism , Colon/microbiology
7.
Biomed Pharmacother ; 176: 116937, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38870632

ABSTRACT

The advent of general anesthesia (GA) has significant implications for clinical practice. However, the exact mechanisms underlying GA-induced transitions in consciousness remain elusive. Given some similarities between GA and sleep, the sleep-arousal neural nuclei and circuits involved in sleep-arousal, including the 5-HTergic system, could be implicated in GA. Herein, we utilized pharmacology, optogenetics, chemogenetics, fiber photometry, and retrograde tracing to demonstrate that both endogenous and exogenous activation of the 5-HTergic neural circuit between the dorsal raphe nucleus (DR) and basolateral amygdala (BLA) promotes arousal and facilitates recovery of consciousness from sevoflurane anesthesia. Notably, the 5-HT1A receptor within this pathway holds a pivotal role. Our findings will be conducive to substantially expanding our comprehension of the neural circuit mechanisms underlying sevoflurane anesthesia and provide a potential target for modulating consciousness, ultimately leading to a reduction in anesthetic dose requirements and side effects.


Subject(s)
Anesthetics, Inhalation , Basolateral Nuclear Complex , Consciousness , Dorsal Raphe Nucleus , Sevoflurane , Sevoflurane/pharmacology , Animals , Dorsal Raphe Nucleus/drug effects , Dorsal Raphe Nucleus/metabolism , Consciousness/drug effects , Anesthetics, Inhalation/pharmacology , Basolateral Nuclear Complex/drug effects , Basolateral Nuclear Complex/metabolism , Basolateral Nuclear Complex/physiology , Male , Mice , Mice, Inbred C57BL , Serotonin/metabolism , Neural Pathways/drug effects , Neural Pathways/physiology , Receptor, Serotonin, 5-HT1A/metabolism , Optogenetics
8.
Zhonghua Yan Ke Za Zhi ; 60(6): 547-558, 2024 Jun 11.
Article in Chinese | MEDLINE | ID: mdl-38825955

ABSTRACT

With the increasing prevalence of myopia among adolescents, the pathogenesis of this condition has garnered significant attention. Studies have discovered the expression of various hormone receptors in ocular tissues of both animals and humans. Additionally, changes in hormone levels accompany the development of myopia, although the exact relationships remain inconclusive. This article reviews the potential influences and mechanisms of action of endogenous hormones such as melatonin, serotonin, insulin, glucagon, sex hormones, vitamin D, and prostaglandins in ocular tissues including the retina, choroid, and sclera. It elaborates on the relationship between fluctuations in these hormone levels and the progression of myopia, aiming to provide guidance for exploring targets for myopia prevention and control.


Subject(s)
Melatonin , Myopia , Humans , Myopia/metabolism , Melatonin/metabolism , Vitamin D/metabolism , Serotonin/metabolism , Insulin/metabolism , Glucagon/metabolism , Animals , Gonadal Steroid Hormones/metabolism , Prostaglandins/metabolism , Hormones/metabolism , Retina/metabolism
9.
Nat Commun ; 15(1): 5042, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38871707

ABSTRACT

Mood disorders are an enigmatic class of debilitating illnesses that affect millions of individuals worldwide. While chronic stress clearly increases incidence levels of mood disorders, including major depressive disorder (MDD), stress-mediated disruptions in brain function that precipitate these illnesses remain largely elusive. Serotonin-associated antidepressants (ADs) remain the first line of therapy for many with depressive symptoms, yet low remission rates and delays between treatment and symptomatic alleviation have prompted skepticism regarding direct roles for serotonin in the precipitation and treatment of affective disorders. Our group recently demonstrated that serotonin epigenetically modifies histone proteins (H3K4me3Q5ser) to regulate transcriptional permissiveness in brain. However, this non-canonical phenomenon has not yet been explored following stress and/or AD exposures. Here, we employed a combination of genome-wide and biochemical analyses in dorsal raphe nucleus (DRN) of male and female mice exposed to chronic social defeat stress, as well as in DRN of human MDD patients, to examine the impact of stress exposures/MDD diagnosis on H3K4me3Q5ser dynamics, as well as associations between the mark and depression-related gene expression. We additionally assessed stress-induced/MDD-associated regulation of H3K4me3Q5ser following AD exposures, and employed viral-mediated gene therapy in mice to reduce H3K4me3Q5ser levels in DRN and examine its impact on stress-associated gene expression and behavior. We found that H3K4me3Q5ser plays important roles in stress-mediated transcriptional plasticity. Chronically stressed mice displayed dysregulated H3K4me3Q5ser dynamics in DRN, with both AD- and viral-mediated disruption of these dynamics proving sufficient to attenuate stress-mediated gene expression and behavior. Corresponding patterns of H3K4me3Q5ser regulation were observed in MDD subjects on vs. off ADs at their time of death. These findings thus establish a neurotransmission-independent role for serotonin in stress-/AD-associated transcriptional and behavioral plasticity, observations of which may be of clinical relevance to human MDD and its treatment.


Subject(s)
Antidepressive Agents , Depressive Disorder, Major , Dorsal Raphe Nucleus , Histones , Stress, Psychological , Animals , Dorsal Raphe Nucleus/metabolism , Dorsal Raphe Nucleus/drug effects , Histones/metabolism , Male , Female , Stress, Psychological/metabolism , Humans , Antidepressive Agents/pharmacology , Depressive Disorder, Major/metabolism , Depressive Disorder, Major/genetics , Depressive Disorder, Major/drug therapy , Mice , Serotonin/metabolism , Mice, Inbred C57BL , Epigenesis, Genetic/drug effects , Behavior, Animal/drug effects , Gene Expression Regulation/drug effects , Social Defeat
10.
J Exp Biol ; 227(12)2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38842023

ABSTRACT

One of the most prevalent axes of behavioral variation in both humans and animals is risk taking, where individuals that are more willing to take risk are characterized as bold while those that are more reserved are regarded as shy. Brain monoamines (i.e. serotonin, dopamine and noradrenaline) have been found to play a role in a variety of behaviors related to risk taking. Using zebrafish, we investigated whether there was a relationship between monoamine function and boldness behavior during exploration of a novel tank. We found a correlation between serotonin metabolism (5-HIAA:5-HT ratio) and boldness during the initial exposure to the tank in female animals. The DOPAC:DA ratio correlated with boldness behavior on the third day in male fish. There was no relationship between boldness and noradrenaline. To probe differences in serotonergic function in bold and shy fish, we administered a selective serotonin reuptake inhibitor, escitalopram, and assessed exploratory behavior. We found that escitalopram had opposing effects on thigmotaxis in bold and shy female animals: the drug caused bold fish to spend more time near the center of the tank and shy fish spent more time near the periphery. Taken together, our findings indicate that variation in serotonergic function has sex-specific contributions to individual differences in risk-taking behavior.


Subject(s)
Individuality , Serotonin , Zebrafish , Animals , Zebrafish/physiology , Zebrafish/metabolism , Female , Serotonin/metabolism , Male , Exploratory Behavior/drug effects , Selective Serotonin Reuptake Inhibitors/pharmacology , Citalopram/pharmacology , Behavior, Animal/drug effects , Risk-Taking , Dopamine/metabolism , Hydroxyindoleacetic Acid/metabolism
11.
PLoS One ; 19(6): e0304910, 2024.
Article in English | MEDLINE | ID: mdl-38837989

ABSTRACT

During lactation, the murine mammary gland is responsible for a significant increase in circulating serotonin. However, the role of mammary-derived serotonin in energy homeostasis during lactation is unclear. To investigate this, we utilized C57/BL6J mice with a lactation and mammary-specific deletion of the gene coding for the rate-limiting enzyme in serotonin synthesis (TPH1, Wap-Cre x TPH1FL/FL) to understand the metabolic contributions of mammary-derived serotonin during lactation. Circulating serotonin was reduced by approximately 50% throughout lactation in Wap-Cre x TPH1FL/FL mice compared to wild-type mice (TPH1FL/FL), with mammary gland and liver serotonin content reduced on L21. The Wap-Cre x TPH1FL/FL mice had less serotonin and insulin immunostaining in the pancreatic islets on L21, resulting in reduced circulating insulin but no changes in glucose. The mammary glands of Wap-Cre x TPH1FL/FL mice had larger mammary alveolar areas, with fewer and smaller intra-lobular adipocytes, and increased expression of milk protein genes (e.g., WAP, CSN2, LALBA) compared to TPH1FL/FL mice. No changes in feed intake, body composition, or estimated milk yield were observed between groups. Taken together, mammary-derived serotonin appears to contribute to the pancreas-mammary cross-talk during lactation with potential implications in the regulation of insulin homeostasis.


Subject(s)
Lactation , Liver , Mammary Glands, Animal , Mice, Inbred C57BL , Serotonin , Tryptophan Hydroxylase , Animals , Lactation/metabolism , Serotonin/metabolism , Female , Mammary Glands, Animal/metabolism , Mice , Liver/metabolism , Tryptophan Hydroxylase/metabolism , Tryptophan Hydroxylase/genetics , Pancreas/metabolism , Insulin/metabolism , Insulin/blood
12.
Int J Mol Sci ; 25(10)2024 May 14.
Article in English | MEDLINE | ID: mdl-38791376

ABSTRACT

Inflammatory bowel disease (IBD) is a chronic inflammatory condition involving dysregulated immune responses and imbalances in the gut microbiota in genetically susceptible individuals. Current therapies for IBD often have significant side-effects and limited success, prompting the search for novel therapeutic strategies. Microbiome-based approaches aim to restore the gut microbiota balance towards anti-inflammatory and mucosa-healing profiles. Extracellular vesicles (EVs) from beneficial gut microbes are emerging as potential postbiotics. Serotonin plays a crucial role in intestinal homeostasis, and its dysregulation is associated with IBD severity. Our study investigated the impact of EVs from the probiotic Nissle 1917 (EcN) and commensal E. coli on intestinal serotonin metabolism under inflammatory conditions using an IL-1ß-induced inflammation model in Caco-2 cells. We found strain-specific effects. Specifically, EcN EVs reduced free serotonin levels by upregulating SERT expression through the downregulation of miR-24, miR-200a, TLR4, and NOD1. Additionally, EcN EVs mitigated IL-1ß-induced changes in tight junction proteins and oxidative stress markers. These findings underscore the potential of postbiotic interventions as a therapeutic approach for IBD and related pathologies, with EcN EVs exhibiting promise in modulating serotonin metabolism and preserving intestinal barrier integrity. This study is the first to demonstrate the regulation of miR-24 and miR-200a by probiotic-derived EVs.


Subject(s)
Escherichia coli , Extracellular Vesicles , Inflammation , Interleukin-1beta , Intestinal Mucosa , MicroRNAs , Probiotics , Serotonin , Humans , Interleukin-1beta/metabolism , Interleukin-1beta/genetics , Extracellular Vesicles/metabolism , Probiotics/pharmacology , Serotonin/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Caco-2 Cells , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Inflammation/metabolism , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/genetics , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/chemically induced , Inflammatory Bowel Diseases/therapy , Nod1 Signaling Adaptor Protein/metabolism , Nod1 Signaling Adaptor Protein/genetics , Epithelial Cells/metabolism , Serotonin Plasma Membrane Transport Proteins/metabolism , Serotonin Plasma Membrane Transport Proteins/genetics , Oxidative Stress , Gene Expression Regulation
13.
Nat Commun ; 15(1): 4307, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811567

ABSTRACT

G protein-coupled receptors (GPCRs) are sophisticated signaling machines able to simultaneously elicit multiple intracellular signaling pathways upon activation. Complete (in)activation of all pathways can be counterproductive for specific therapeutic applications. This is the case for the serotonin 2 A receptor (5-HT2AR), a prominent target for the treatment of schizophrenia. In this study, we elucidate the complex 5-HT2AR coupling signature in response to different signaling probes, and its physiological consequences by combining computational modeling, in vitro and in vivo experiments with human postmortem brain studies. We show how chemical modification of the endogenous agonist serotonin dramatically impacts the G protein coupling profile of the 5-HT2AR and the associated behavioral responses. Importantly, among these responses, we demonstrate that memory deficits are regulated by Gαq protein activation, whereas psychosis-related behavior is modulated through Gαi1 stimulation. These findings emphasize the complexity of GPCR pharmacology and physiology and open the path to designing improved therapeutics for the treatment of stchizophrenia.


Subject(s)
Memory Disorders , Psychotic Disorders , Receptor, Serotonin, 5-HT2A , Serotonin , Animals , Female , Humans , Male , Mice , Brain/metabolism , GTP-Binding Protein alpha Subunits, Gq-G11/metabolism , GTP-Binding Protein alpha Subunits, Gq-G11/genetics , HEK293 Cells , Memory Disorders/metabolism , Psychotic Disorders/metabolism , Psychotic Disorders/drug therapy , Receptor, Serotonin, 5-HT2A/metabolism , Schizophrenia/metabolism , Serotonin/metabolism , Signal Transduction
14.
J Med Life ; 17(2): 133-140, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38813365

ABSTRACT

Surgical interventions, such as laparoscopic sleeve gastrectomy (LSG), are frequently associated with significant weight loss. However, the initiation and maintenance of this weight reduction are multifaceted processes influenced by genetic, psychological, behavioral, dietary, and metabolic factors. This review examined the role of metabolic hormones, specifically serotonin, in sustaining weight loss post-LSG. A systematic evaluation of six research articles obtained from Scopus, PubMed, and Cochrane was conducted, focusing on the role of serotonin in weight loss maintenance. We included randomized controlled trials involving adults over 18 years. Studies lacking an intensive weight regulation approach were excluded. Information was systematically extracted and analyzed from the selected studies, with data on intervention and control groups summarized in tables to compare outcomes one year post-LSG. The findings revealed a complex interplay between serotonin and its role in weight maintenance after sleeve gastrectomy. While some studies demonstrated successful weight loss maintenance with serotonin intervention, the systematic review found no association between serotonin and weight loss maintenance. Factors beyond serotonin levels, including individual motivation, behavioral strategies, and physical activity, were identified as crucial contributors to sustained weight loss. While the results may not demonstrate a recognizable association between serotonin and weight loss maintenance, the significance of this review lies in its contribution to the existing body of knowledge. By synthesizing current evidence, the study adds a nuanced perspective to understanding factors influencing post-LSG outcomes.


Subject(s)
Gastrectomy , Serotonin , Weight Loss , Humans , Serotonin/metabolism , Gastrectomy/methods
15.
Sci Rep ; 14(1): 10190, 2024 05 03.
Article in English | MEDLINE | ID: mdl-38702366

ABSTRACT

Dysfunction of central serotonergic neurons is known to cause depressive disorders in humans, who often show reproductive and/or glucose metabolism disorders. This study examined whether dorsal raphe (DR) serotonergic neurons sense high glucose availability to upregulate reproductive function via activating hypothalamic arcuate (ARC) kisspeptin neurons (= KNDy neurons), a dominant stimulator of gonadotropin-releasing hormone (GnRH)/gonadotropin pulses, using female rats and goats. RNA-seq and histological analysis revealed that stimulatory serotonin-2C receptor (5HT2CR) was mainly expressed in the KNDy neurons in female rats. The serotonergic reuptake inhibitor administration into the mediobasal hypothalamus (MBH), including the ARC, significantly blocked glucoprivic suppression of luteinizing hormone (LH) pulses and hyperglycemia induced by intravenous 2-deoxy-D-glucose (2DG) administration in female rats. A local infusion of glucose into the DR significantly increased in vivo serotonin release in the MBH and partly restored LH pulses and hyperglycemia in the 2DG-treated female rats. Furthermore, central administration of serotonin or a 5HT2CR agonist immediately evoked GnRH pulse generator activity, and central 5HT2CR antagonism blocked the serotonin-induced facilitation of GnRH pulse generator activity in ovariectomized goats. These results suggest that DR serotonergic neurons sense high glucose availability to reduce gluconeogenesis and upregulate reproductive function by activating GnRH/LH pulse generator activity in mammals.


Subject(s)
Glucose , Goats , Gonadotropin-Releasing Hormone , Luteinizing Hormone , Receptor, Serotonin, 5-HT2C , Serotonergic Neurons , Animals , Luteinizing Hormone/metabolism , Female , Receptor, Serotonin, 5-HT2C/metabolism , Rats , Serotonergic Neurons/metabolism , Gonadotropin-Releasing Hormone/metabolism , Glucose/metabolism , Serotonin/metabolism , Kisspeptins/metabolism , Arcuate Nucleus of Hypothalamus/metabolism , Arcuate Nucleus of Hypothalamus/drug effects , Dorsal Raphe Nucleus/metabolism , Dorsal Raphe Nucleus/drug effects , Rats, Sprague-Dawley
16.
Mol Pain ; 20: 17448069241254455, 2024.
Article in English | MEDLINE | ID: mdl-38728068

ABSTRACT

Pruritis, the sensation of itch, is produced by multiple substances, exogenous and endogenous, that sensitizes specialized sensory neurons (pruriceptors and pruri-nociceptors). Unfortunately, many patients with acute and chronic pruritis obtain only partial relief when treated with currently available treatment modalities. We recently demonstrated that the topical application of high molecular weight hyaluronan (HMWH), when combined with vehicles containing transdermal transport enhancers, produce potent long-lasting reversal of nociceptor sensitization associated with inflammatory and neuropathic pain. In the present experiments we tested the hypothesis that the topical formulation of HMWH with protamine, a transdermal transport enhancer, can also attenuate pruritis. We report that this topical formulation of HMWH markedly attenuates scratching behavior at the nape of the neck induced by serotonin (5-hydroxytryptamine, 5-HT), in male and female rats. Our results support the hypothesis that topical HMWH in a transdermal transport enhancer vehicle is a strong anti-pruritic.


Subject(s)
Administration, Cutaneous , Hyaluronic Acid , Protamines , Rats, Sprague-Dawley , Animals , Hyaluronic Acid/pharmacology , Hyaluronic Acid/chemistry , Male , Female , Rats , Protamines/pharmacology , Molecular Weight , Serotonin/metabolism , Administration, Topical
17.
Front Endocrinol (Lausanne) ; 15: 1331231, 2024.
Article in English | MEDLINE | ID: mdl-38694940

ABSTRACT

A subset of neuroendocrine tumors (NETs) can cause an excessive secretion of hormones, neuropeptides, and biogenic amines into the bloodstream. These so-called functional NETs evoke a hormone-related disease and lead to several different syndromes, depending on the factors released. One of the most common functional syndromes, carcinoid syndrome, is characterized mainly by over-secretion of serotonin. However, what distinguishes functional from non-functional tumors on a molecular level remains unknown. Here, we demonstrate that the expression of sortilin, a widely expressed transmembrane receptor involved in intracellular protein sorting, is significantly increased in functional compared to non-functional NETs and thus can be used as a biomarker for functional NETs. Furthermore, using a cell line model of functional NETs, as well as organoids, we demonstrate that inhibition of sortilin reduces cellular serotonin concentrations and may therefore serve as a novel therapeutic target to treat patients with carcinoid syndrome.


Subject(s)
Adaptor Proteins, Vesicular Transport , Neuroendocrine Tumors , Serotonin , Female , Humans , Male , Adaptor Proteins, Vesicular Transport/metabolism , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Malignant Carcinoid Syndrome/metabolism , Neuroendocrine Tumors/metabolism , Neuroendocrine Tumors/pathology , Serotonin/metabolism , Middle Aged , Animals , Mice
18.
Psychiatry Res ; 337: 115951, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38735240

ABSTRACT

Isolation of rodents throughout adolescence is known to induce many behavioral abnormalities which resemble neuropsychiatric disorders. Separately, this paradigm has also been shown to induce long-term metabolic changes consistent with a pre-diabetic state. Here, we investigate changes in central serotonin (5-HT) and glucagon-like peptide 1 (GLP-1) neurobiology that dually accompany behavioral and metabolic outcomes following social isolation stress throughout adolescence. We find that adolescent-isolation mice exhibit elevated blood glucose levels, impaired peripheral insulin signaling, altered pancreatic function, and fattier body composition without changes in bodyweight. These mice further exhibited disruptions in sleep and enhanced nociception. Using bulk and spatial transcriptomic techniques, we observe broad changes in neural 5-HT, GLP-1, and appetitive circuits. We find 5-HT neurons of adolescent-isolation mice to be more excitable, transcribe fewer copies of Glp1r (mRNA; GLP-1 receptor), and demonstrate resistance to the inhibitory effects of the GLP-1R agonist semaglutide on action potential thresholds. Surprisingly, we find that administration of semaglutide, commonly prescribed to treat metabolic syndrome, induced deficits in social interaction in group-housed mice and rescued social deficits in isolated mice. Overall, we find that central 5-HT circuitry may simultaneously influence mental well-being and metabolic health in this model, via interactions with GLP-1 and proopiomelanocortin circuitry.


Subject(s)
Disease Models, Animal , Glucagon-Like Peptide 1 , Glucagon-Like Peptide-1 Receptor , Serotonin , Social Isolation , Animals , Mice , Glucagon-Like Peptide 1/metabolism , Glucagon-Like Peptide-1 Receptor/metabolism , Male , Serotonin/metabolism , Mental Disorders/metabolism , Mental Disorders/drug therapy , Mice, Inbred C57BL , Metabolic Diseases/metabolism , Metabolic Diseases/physiopathology , Blood Glucose/metabolism , Blood Glucose/drug effects
19.
J Tradit Chin Med ; 44(3): 537-544, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38767638

ABSTRACT

OBJECTIVE: To explore the early hemostatic mechanism of Jianpi Yiqi Shexue decoction (, JYSD) in treating immune thrombocytopathy (ITP), based on the functional homeostasis of brain-intestine axis and blood neurotransmitter METHODS: Non-drug treatment cases: Healthy volunteers were selected as normal control group and compared with patients with dysfunctional uterine bleeding, gastrointestinal tumors with bleeding and ITP, to detect the changes of blood 5-hydroxytryptamine (5-HT), ß-endorphin (ß-EP), vasoactive intestinal peptide (VIP) and compare the changes of blood neuro-transmitters in patients with different disease symptoms. Drug treatment cases: According to the randomized controlled multicenter clinical trial, 272 ITP patients were randomly divided into three groups: treatment group (JYSD) combined group (JYSD + Prednisone) control group (Prednisone). The changes of blood neuro-transmitter (5-HT, ß-EP, VIP) before and after treatment were detected on the basis of peripheral blood platelet (PLT) and grade score. RESULTS: Non-drug treatment cases: compared with the normal control group, the 5-HT level was higher, and the VIP and ß-EP levels were both lower in the ITP group (P < 0.001), and the 5-HT, VIP and ß-EP levels in the Gastrointestinal tumors with bleeding group were also lower compared with the normal control group (P < 0.05, 0.001). Drug treatment cases: The PLT grading scores of the combination group and the control group after treatment were lower than that before treatment (P < 0.05, 0.001). The PLT grading score of the 3 groups were compared in pairs after treatment: the combination group was the lowest among the 3 groups, which was better than the treatment group, but no better than the control group (vs the treatment group, P = 0.005, vs the control group, P = 0.709). The statistical results of full analysis set (FAS) and per protocol set (PPS) were consistent. The bleeding symptom scores of the treatment and combination groups began to drop 7 d after treatment, and kept dropping 14 d after treatment until the end of the study (P < 0.05). On the other hand, the control group started to show favorable results 14 d after treatment (P < 0.05). The FAS and PPS analysis results were consistent. In the control group, the 5-HT level was higher and VIP level was lower after treatment, compared with those before treatment (P < 0.05, 0.001). The ß-EP levels were both increased in the treatment and combination group after treatment, compared with those before treatment (P < 0.05). After treatment, the ß-EP levels in the treatment and control groups were significantly lower compared with the combination groups (P < 0.05). After treatment, compared with the control group, the VIP levels in the treatment and combination groups were up-regulated, and the differences were statistically significant by rank sum test (P < 0.01), and by t-test (P = 0.0002, 0.0001). CONCLUSIONS: The prednisone tablet is better than the JYSD in increasing the level of PLT, while prednisone tablet combined with JYSD has more advantages in improving patients' peripheral blood PLT levels. However, in improving the bleeding time of ITP patients, the combination of the two drugs was significantly delayed compared with the single usage, showing the characteristics and advantages of traditional Chinese medicine. JYSD can regulate the neurotransmitter level of ITP patients through the function of the brain-gut axis, mobilize 5-HT in the blood of ITP patients to promote the contraction of blood vessels and smooth muscles, and activate the coagulation mechanism are the early hemostatic mechanisms of JYSD. Up-regulate the levels of ß-EP and balancing VIP levels may be an important part of the immune mechanism of JYSD for regulating ITP patients.


Subject(s)
Drugs, Chinese Herbal , Serotonin , Humans , Drugs, Chinese Herbal/administration & dosage , Female , Middle Aged , Adult , Male , Serotonin/blood , Aged , Young Adult , Vasoactive Intestinal Peptide/blood , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/blood , beta-Endorphin/blood , Adolescent , Hemostatics/administration & dosage , Hemostasis/drug effects
20.
Brain Res ; 1838: 148996, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38744387

ABSTRACT

INTRODUCTION: The excessive fat accumulation in obesity, resulting from an unbalanced diet, can lead to metabolic and neurological disorders and increase the risk of developing anxiety and depression. AIM: Assess the impact of dietary intervention (DI) on the serotonergic system, brain-derived neurotrophic factor (BDNF) expression and behaviors of obese mice. METHODS: Male C57BL/6 mice, 5 weeks old, received a high-fat diet (HFD) for 10 weeks for the induction of obesity. After this period, for 8 weeks, half of these animals received a control diet (CD), group obese (OB) + control diet (OB + CD, n = 10), and another half continued being fed HFD, group obese + HFD (OB + HFD, n = 10). At the end of the eighth week of intervention, behavioral tests were performed (sucrose preference test, open field, novel object recognition, elevated plus maze and tail suspension). Body weight and food intake were assessed weekly. Visceral adiposity, the hippocampal and hypothalamic protein expression of BDNF, 5-HT1A (5-HT1A serotonin receptor) and TPH2 (key enzyme in serotonin synthesis), were evaluated after euthanasia. RESULTS: The dietary intervention involved changing from a HFD to a CD over an 8-week period, effectively reduced body weight gain, adiposity, and anhedonia-like behavior. In the OB + HFD group, we saw a lower sucrose preference and shorter traveled distance in the open field, along with increased pro-BDNF expression in the hypothalamus compared to the OB + CD mice. However, the levels of TPH2 and 5-HT1A remained unchanged. CONCLUSION: The HFD model induced both obesity and anhedonia, but the dietary intervention successfully improved these conditions.


Subject(s)
Adiposity , Anhedonia , Body Weight , Brain-Derived Neurotrophic Factor , Diet, High-Fat , Mice, Inbred C57BL , Obesity , Serotonin , Animals , Brain-Derived Neurotrophic Factor/metabolism , Male , Anhedonia/physiology , Serotonin/metabolism , Obesity/metabolism , Diet, High-Fat/adverse effects , Adiposity/physiology , Mice , Body Weight/physiology , Mice, Obese , Hippocampus/metabolism , Receptor, Serotonin, 5-HT1A/metabolism , Tryptophan Hydroxylase/metabolism , Behavior, Animal/physiology , Hypothalamus/metabolism , Dietary Patterns
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