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1.
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
2.
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
3.
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
4.
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
5.
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
6.
Cogn Sci ; 48(5): e13452, 2024 05.
Article in English | MEDLINE | ID: mdl-38742272

ABSTRACT

Slower perceptual alternations, a notable perceptual effect observed in psychiatric disorders, can be alleviated by antidepressant therapies that affect serotonin levels in the brain. While these phenomena have been well documented, the underlying neurocognitive mechanisms remain to be elucidated. Our study bridges this gap by employing a computational cognitive approach within a Bayesian predictive coding framework to explore these mechanisms in depression. We fitted a prediction error (PE) model to behavioral data from a binocular rivalry task, uncovering that significantly higher initial prior precision and lower PE led to a slower switch rate in patients with depression. Furthermore, serotonin-targeting antidepressant treatments significantly decreased the prior precision and increased PE, both of which were predictive of improvements in the perceptual alternation rate of depression patients. These findings indicated that the substantially slower perception switch rate in patients with depression was caused by the greater reliance on top-down priors and that serotonin treatment's efficacy was in its recalibration of these priors and enhancement of PE. Our study not only elucidates the cognitive underpinnings of depression, but also suggests computational modeling as a potent tool for integrating cognitive science with clinical psychology, advancing our understanding and treatment of cognitive impairments in depression.


Subject(s)
Bayes Theorem , Depression , Humans , Male , Female , Adult , Visual Perception , Antidepressive Agents/therapeutic use , Serotonin/metabolism , Middle Aged
7.
Sci Rep ; 14(1): 10479, 2024 05 07.
Article in English | MEDLINE | ID: mdl-38714793

ABSTRACT

Enterochromaffin (EC) cells located within the intestinal mucosal epithelium release serotonin (5-HT) to regulate motility tones, barrier function and the immune system. Electroanalytical methodologies have been able to monitor steady state basal extracellular 5-HT levels but are unable to provide insight into how these levels are influenced by key regulatory processes such as release and uptake. We established a new measurement approach, amperometry approach curve profiling, which monitors the extracellular 5-HT level at different electrode-tissue (E-T) distances. Analysis of the current profile can provide information on contributions of regulatory components on the observed extracellular 5-HT level. Measurements were conducted from ex vivo murine ileum and colon using a boron-doped diamond (BDD) microelectrode. Amperometry approach curve profiling coupled with classical pharmacology demonstrated that extracellular 5-HT levels were significantly lower in the colon when compared to the ileum. This difference was due to a greater degree of activity of the 5-HT transporter (SERT) and a reduced amount of 5-HT released from colonic EC cells. The presence of an inhibitory 5-HT4 autoreceptor was observed in the colon, where a 40% increase in extracellular 5-HT was the half maximal inhibitory concentration for activation of the autoreceptor. This novel electroanalytical approach allows estimates of release and re-uptake and their contribution to 5-HT extracellular concentration from intestinal tissue be obtained from a single series of measurements.


Subject(s)
Colon , Ileum , Intestinal Mucosa , Serotonin , Serotonin/metabolism , Animals , Mice , Ileum/metabolism , Intestinal Mucosa/metabolism , Colon/metabolism , Enterochromaffin Cells/metabolism , Microelectrodes , Serotonin Plasma Membrane Transport Proteins/metabolism , Male , Electrochemical Techniques/methods , Mice, Inbred C57BL
8.
Cell Commun Signal ; 22(1): 266, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38741139

ABSTRACT

Glioblastoma (GBM) is a type of brain cancer categorized as a high-grade glioma. GBM is characterized by limited treatment options, low patient survival rates, and abnormal serotonin metabolism. Previous studies have investigated the tumor suppressor function of aldolase C (ALDOC), a glycolytic enzyme in GBM. However, it is unclear how ALDOC regulates production of serotonin and its associated receptors, HTRs. In this study, we analyzed ALDOC mRNA levels and methylation status using sequencing data and in silico datasets. Furthermore, we investigated pathways, phenotypes, and drug effects using cell and mouse models. Our results suggest that loss of ALDOC function in GBM promotes tumor cell invasion and migration. We observed that hypermethylation, which results in loss of ALDOC expression, is associated with serotonin hypersecretion and the inhibition of PPAR-γ signaling. Using several omics datasets, we present evidence that ALDOC regulates serotonin levels and safeguards PPAR-γ against serotonin metabolism mediated by 5-HT, which leads to a reduction in PPAR-γ expression. PPAR-γ activation inhibits serotonin release by HTR and diminishes GBM tumor growth in our cellular and animal models. Importantly, research has demonstrated that PPAR-γ agonists prolong animal survival rates and increase the efficacy of temozolomide in an orthotopic brain model of GBM. The relationship and function of the ALDOC-PPAR-γ axis could serve as a potential prognostic indicator. Furthermore, PPAR-γ agonists offer a new treatment alternative for glioblastoma multiforme (GBM).


Subject(s)
Glioblastoma , PPAR gamma , Temozolomide , Temozolomide/pharmacology , Temozolomide/therapeutic use , Glioblastoma/drug therapy , Glioblastoma/pathology , Glioblastoma/genetics , Glioblastoma/metabolism , Humans , Animals , PPAR gamma/metabolism , Mice , Cell Line, Tumor , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Disease Progression , Serotonin/metabolism , Signal Transduction/drug effects , Antineoplastic Agents, Alkylating/pharmacology , Antineoplastic Agents, Alkylating/therapeutic use , Gene Expression Regulation, Neoplastic/drug effects , PPAR-gamma Agonists
9.
Article in English | MEDLINE | ID: mdl-38765505

ABSTRACT

Objective: To evaluate whether the continuous support provided by doulas influences the endogenous release of serotonin in parturients. Methods: This pilot study included 24 primigravidae at term. Of these, 12 women received continuous doula support (Experimental Group), whereas the other 12 received the usual assistance without doula support (Control Group). Blood samples were collected from all the women at the active and expulsion stages of labor and at the fourth period of labor (Greenberg period) for evaluation of their serotonin levels using high-performance liquid chromatography. Results: The average serotonin concentrations in the control and experimental groups were respectively 159.33 and 150.02 ng/mL at the active stage, 179.13 and 162.65 ng/mL at the expulsion stage, and 198.94 and 221.21 ng/mL at the Greenberg period. There were no statistically significant differences in serotonin concentrations between the two groups at the active and expulsion stages of labor. By contrast, within the experimental group, a significant increase in serotonin concentration was observed in the Greenberg period compared with the levels in the active and expulsion stages (p < 0.05). Conclusion: The novelty of this study relies on the ability to correlate the influence of the continuous support offered by doulas with the release of serotonin in parturients, with the results suggesting that the assistance received during labor can modulate the levels of hormone release in the Greenberg period. Brazilian Registry of Clinical Trials: RBR-4zjjm4h.


Subject(s)
Serotonin , Humans , Female , Pilot Projects , Serotonin/blood , Pregnancy , Adult , Doulas , Young Adult , Labor, Obstetric
10.
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
11.
J Phys Chem B ; 128(20): 4975-4985, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38743687

ABSTRACT

The primary event in chemical neurotransmission involves the fusion of a membrane-limited vesicle at the plasma membrane and the subsequent release of its chemical neurotransmitter cargo. The cargo itself is not known to have any effect on the fusion event. However, amphiphilic monoamine neurotransmitters (e.g., serotonin and dopamine) are known to strongly interact with lipid bilayers and to affect their mechanical properties, which can in principle impact membrane-mediated processes. Here, we probe whether serotonin can enhance the association and fusion of artificial lipid vesicles in vitro. We employ fluorescence correlation spectroscopy and total internal reflection fluorescence microscopy to measure the attachment and fusion of vesicles whose lipid compositions mimic the major lipid components of synaptic vesicles. We find that the association between vesicles and supported lipid bilayers is strongly enhanced in a serotonin dose-dependent manner, and this drives an increase in the rate of spontaneous fusion. Molecular dynamics simulations and fluorescence spectroscopy data show that serotonin insertion increases the water content of the hydrophobic part of the bilayer. This suggests that the enhanced membrane association is likely driven by an energetically favorable drying transition. Other monoamines, such as dopamine and norepinephrine, but not other related species, such as tryptophan, show similar effects on membrane association. Our results reveal a lipid bilayer-mediated mechanism by which monoamines can themselves modulate vesicle fusion, potentially adding to the control toolbox for the tightly regulated process of neurotransmission in vivo.


Subject(s)
Lipid Bilayers , Molecular Dynamics Simulation , Serotonin , Lipid Bilayers/chemistry , Lipid Bilayers/metabolism , Serotonin/chemistry , Serotonin/metabolism , Membrane Fusion , Synaptic Vesicles/metabolism , Synaptic Vesicles/chemistry , Spectrometry, Fluorescence , Hydrophobic and Hydrophilic Interactions
12.
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
13.
Int J Mol Sci ; 25(9)2024 May 03.
Article in English | MEDLINE | ID: mdl-38732220

ABSTRACT

Serotonin is an essential neuromodulator for mental health and animals' socio-cognitive abilities. However, we previously found that a constitutive depletion of central serotonin did not impair rat cognitive abilities in stand-alone tests. Here, we investigated how a mild and acute decrease in brain serotonin would affect rats' cognitive abilities. Using a novel rat model of inducible serotonin depletion via the genetic knockdown of tryptophan hydroxylase 2 (TPH2), we achieved a 20% decrease in serotonin levels in the hypothalamus after three weeks of non-invasive oral doxycycline administration. Decision making, cognitive flexibility, and social recognition memory were tested in low-serotonin (Tph2-kd) and control rats. Our results showed that the Tph2-kd rats were more prone to choose disadvantageously in the long term (poor decision making) in the Rat Gambling Task and that only the low-serotonin poor decision makers were more sensitive to probabilistic discounting and had poorer social recognition memory than other low-serotonin and control individuals. Flexibility was unaffected by the acute brain serotonin reduction. Poor social recognition memory was the most central characteristic of the behavioral network of low-serotonin poor decision makers, suggesting a key role of social recognition in the expression of their profile. The acute decrease in brain serotonin appeared to specifically amplify the cognitive impairments of the subgroup of individuals also identified as poor decision makers in the population. This study highlights the great opportunity the Tph2-kd rat model offers to study inter-individual susceptibilities to develop cognitive impairment following mild variations of brain serotonin in otherwise healthy individuals. These transgenic and differential approaches together could be critical for the identification of translational markers and vulnerabilities in the development of mental disorders.


Subject(s)
Decision Making , Serotonin , Tryptophan Hydroxylase , Animals , Tryptophan Hydroxylase/metabolism , Tryptophan Hydroxylase/genetics , Serotonin/metabolism , Rats , Male , Social Behavior , Gene Knockdown Techniques , Behavior, Animal , Cognition , Hypothalamus/metabolism
14.
Medicine (Baltimore) ; 103(19): e38180, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728460

ABSTRACT

BACKGROUND: Poststroke depression (PSD) is one of the most common stroke complications. It not only leads to a decline in patients' quality of life but also increases the mortality of patients. In this study, the method of combining Chinese traditional exercise Baduanjin with psychotherapy was used to intervene in patients with PSD and to explore the improvement of sleep, mood, and serum levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) levels in patients with PSD by combined treatment. METHODS: A total of 100 patients with PSD who met the inclusion criteria were randomly assigned to Baduanjin group (n = 50) or control group (n = 50). The control group received treatment with escitalopram oxalate and rational emotive behavior therapy, while the experimental group received Baduanjin training in addition to the treatment given to the control group. Changes in sleep efficiency, sleep total time, sleep latency, arousal index, Hamilton Anxiety Rating Scale, Hamilton Depression Scale score, serum BDNF, 5-HT, IL-6 levels, and Modified Barthel Index were measured at baseline, 4 weeks and 8 weeks after intervention, and the results were compared between the 2 groups. RESULTS: Significantly improvements in the sleep efficiency, sleep total time, serum 5-HT, BDNF levels, and Modified Barthel Index score were detected at week 4 in the Baduanjin group than in the control group (P < .05). Additionally, the sleep latency, arousal index, Hamilton Anxiety Rating Scale, Hamilton Depression Scale scores and IL-6 levels in the Baduanjin group were lower than those in the control group (P < .05). After 8 weeks of treatment, the above indexes in the Baduanjin group were further improved compared with the control group (P < .05), and the above indexes of the 2 groups were significantly improved compared with the baseline (P < .001). CONCLUSION: Baduanjin exercise combined with rational emotive behavior therapy effectively improves the mood and sleep status of patients with PSD; It increases the serum levels of 5-HT and BDNF while reducing the level of serum proinflammatory factor IL-6; additionally, the intervention alleviates the degree of neurological impairment, upgrades the ability of daily living, and improves the quality of life.


Subject(s)
Affect , Brain-Derived Neurotrophic Factor , Depression , Sleep , Stroke , Humans , Male , Female , Middle Aged , Stroke/complications , Stroke/psychology , Stroke/therapy , Brain-Derived Neurotrophic Factor/blood , Depression/therapy , Depression/etiology , Aged , Interleukin-6/blood , Behavior Therapy/methods , Serotonin/blood , Combined Modality Therapy , Exercise Therapy/methods , Medicine, Chinese Traditional/methods , Treatment Outcome
15.
Synapse ; 78(3): e22291, 2024 May.
Article in English | MEDLINE | ID: mdl-38733105

ABSTRACT

Spinal serotonin enables neuro-motor recovery (i.e., plasticity) in patients with debilitating paralysis. While there exists time of day fluctuations in serotonin-dependent spinal plasticity, it is unknown, in humans, whether this is due to dynamic changes in spinal serotonin levels or downstream signaling processes. The primary objective of this study was to determine if time of day variations in spinal serotonin levels exists in humans. To assess this, intrathecal drains were placed in seven adults with cerebrospinal fluid (CSF) collected at diurnal (05:00 to 07:00) and nocturnal (17:00 to 19:00) intervals. High performance liquid chromatography with mass spectrometry was used to quantify CSF serotonin levels with comparisons being made using univariate analysis. From the 7 adult patients, 21 distinct CSF samples were collected: 9 during the diurnal interval and 12 during nocturnal. Diurnal CSF samples demonstrated an average serotonin level of 216.6 ± $ \pm $ 67.7 nM. Nocturnal CSF samples demonstrated an average serotonin level of 206.7 ± $ \pm $ 75.8 nM. There was no significant difference between diurnal and nocturnal CSF serotonin levels (p = .762). Within this small cohort of spine healthy adults, there were no differences in diurnal versus nocturnal spinal serotonin levels. These observations exclude spinal serotonin levels as the etiology for time of day fluctuations in serotonin-dependent spinal plasticity expression.


Subject(s)
Circadian Rhythm , Serotonin , Humans , Serotonin/cerebrospinal fluid , Male , Adult , Female , Circadian Rhythm/physiology , Middle Aged , Spinal Cord/metabolism , Chromatography, High Pressure Liquid , Aged
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.
Int J Mol Sci ; 25(9)2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38731967

ABSTRACT

Tryptophan metabolites, such as 5-hydroxytryptophan (5-HTP), serotonin, and melatonin, hold significant promise as supplements for managing various mood-related disorders, including depression and insomnia. However, their chemical production via chemical synthesis and phytochemical extraction presents drawbacks, such as the generation of toxic byproducts and low yields. In this study, we explore an alternative approach utilizing S. cerevisiae STG S101 for biosynthesis. Through a series of eleven experiments employing different combinations of tryptophan supplementation, Tween 20, and HEPES buffer, we investigated the production of these indolamines. The tryptophan metabolites were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Notably, setups replacing peptone in the YPD media with tryptophan (Run 3) and incorporating tryptophan along with 25 mM HEPES buffer (Run 4) demonstrated successful biosynthesis of 5-HTP and serotonin. The highest 5-HTP and serotonin concentrations were 58.9 ± 16.0 mg L-1 and 0.0650 ± 0.00211 mg L-1, respectively. Melatonin concentrations were undetected in all the setups. These findings underscore the potential of using probiotic yeast strains as a safer and conceivably more cost-effective alternative for indolamine synthesis. The utilization of probiotic strains presents a promising avenue, potentially offering scalability, sustainability, reduced environmental impact, and feasibility for large-scale production.


Subject(s)
5-Hydroxytryptophan , Biosynthetic Pathways , Saccharomyces cerevisiae , Serotonin , Tryptophan , Tryptophan/metabolism , Saccharomyces cerevisiae/metabolism , Serotonin/metabolism , Serotonin/biosynthesis , 5-Hydroxytryptophan/metabolism , Melatonin/metabolism , Melatonin/biosynthesis , Tandem Mass Spectrometry , Chromatography, Liquid/methods
18.
Georgian Med News ; (348): 87-90, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38807398

ABSTRACT

Selective degeneration of motoneurons is the pathological hallmark of amyotrophic lateral sclerosis (ALS). Does serotonin (5-HT) play a role in progression or development of disease is under the research. The topic of the present paper is pressing as there is no data available regarding the spread of amyotrophic lateral sclerosis. It is also noteworthy that previous studies have indicated that the pathogenesis of ALS is closely linked to 5-hydroxytryptamine (5-HT). The clinical research was conducted in Georgia. During the last five years, 60 patients from different parts of Georgia have been studied, searched, and examined by us. Including from Samegrolo, Kartli, Adjara, Abkhazia, Guria, Kakheti regions. The Georgian Neurologists Corps participated and helped us in finding patients. Brain MRI and electromyography were also performed. 60 patients with different forms of ALS participated in the study, including 34 (56.66%) men and 26 (43.33%) women. Their age ranges from 30 to 81 years. The study was conducted after obtaining the written consent of the patients, taking into account the ethical requirements for the study. We also compared the results of the serotonin level of patients with amyotrophic lateral sclerosis with a control group of 20 people (aged 18 to 50 years) who had no neurological disease in past medical history. Patients of the first group, with LMN damage, are observed with decreased amount of serotonin (61.3) %, compared to other pairs, followed by patients of the upper neuron and bulbar syndrome groups, the level of serotonin in the control group is quite high. Thus, the level of serotonin in the group of patients with bulbar events is higher than in the other groups. Low serotonin requires further investigation. According to our research, the longer the anamnesis of amyotrophic lateral sclerosis patients is, the lower the level of serotonin is observed. It should also be taken into account that a low level of serotonin may be due to the presence of depression, which requires additional research. We speculate that 5-HT could therefore be a potential therapeutic target for amyotrophic lateral sclerosis.


Subject(s)
Amyotrophic Lateral Sclerosis , Serotonin , Humans , Amyotrophic Lateral Sclerosis/pathology , Serotonin/metabolism , Middle Aged , Female , Male , Adult , Aged , Aged, 80 and over , Adolescent , Motor Neurons/pathology , Electromyography , Magnetic Resonance Imaging
19.
BMC Complement Med Ther ; 24(1): 198, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773460

ABSTRACT

BACKGROUND: Yokukansan, a traditional Japanese medicine (Kampo), has been widely used to treat neurosis, dementia, and chronic pain. Previous in vitro studies have suggested that Yokukansan acts as a partial agonist of the 5-HT1A receptor, resulting in amelioration of chronic pain through inhibition of nociceptive neuronal activity. However, its effectiveness for treating postoperative pain remains unknown, although its analgesic mechanism of action has been suggested to involve serotonin and glutamatergic neurotransmission. This study aimed to investigate the effect of Yokukansan on postoperative pain in an animal model. METHODS: A mouse model of postoperative pain was created by plantar incision, and Yokukansan was administered orally the day after paw incision. Pain thresholds for mechanical and heat stimuli were examined in a behavioral experiment. In addition, to clarify the involvement of the serotonergic nervous system, we examined the analgesic effects of Yokukansan in mice that were serotonin-depleted by para-chlorophenylalanine (PCPA) treatment and intrathecal administration of NAN-190, 5-HT1A receptor antagonist. RESULTS: Orally administered Yokukansan increased the pain threshold dose-dependent in postoperative pain model mice. Pretreatment of para-chlorophenylalanine dramatically suppressed serotonin immunoreactivity in the spinal dorsal horn without changing the pain threshold after the paw incision. The analgesic effect of Yokukansan tended to be attenuated by para-chlorophenylalanine pretreatment and significantly attenuated by intrathecal administration of 2.5 µg of NAN-190 compared to that in postoperative pain model mice without para-chlorophenylalanine treatment and NAN-190 administration. CONCLUSION: This study demonstrated that oral administration of Yokukansan has acute analgesic effects in postoperative pain model mice. Behavioral experiments using serotonin-depleted mice and mice intrathecally administered with a 5-HT1A receptor antagonist suggested that Yokukansan acts as an agonist at the 5-HT1A receptor, one of the serotonin receptors, to produce analgesia.


Subject(s)
Analgesics , Disease Models, Animal , Drugs, Chinese Herbal , Pain, Postoperative , Animals , Mice , Drugs, Chinese Herbal/pharmacology , Male , Pain, Postoperative/drug therapy , Analgesics/pharmacology , Serotonin/metabolism , Receptor, Serotonin, 5-HT1A/metabolism , Receptor, Serotonin, 5-HT1A/drug effects , Administration, Oral , Mice, Inbred ICR
20.
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
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