31,462 results on '"Serotonin metabolism"'
Search Results
2. Day time-restricted feeding shows differential synchronizing effects on age-related changes of serotonin metabolism in SCN and the pineal gland in male Wistar rats.
- Author
-
Reddy, V. D. K., Dalai, Minurani, Khan, M. Sultan, and Jagota, Anita
- Abstract
The circadian timing system is synchronized by the environmental photic and non-photic signals. Light is the major cue that entrains the master circadian oscillator located in suprachiasmatic nucleus (SCN). With aging condition ocular light impairs because of the age-related deficiencies in the eye as a result the clock becomes less sensitive to light. In such case non-photic cues may play a major role in synchronizing the clock. Earlier studies have linked altered meal timings to induce many physiological changes including serotonin in different brain regions such as hypothalamus, brain stem and striatum. Much is not known about the effect of timed food restriction as a non-photic stimulus on serotonergic system in SCN under aging condition. We report here the synchronizing effects of time-restricted feeding (TRF) as a non-photic stimulus on serotonin and its related metabolites in the SCN and pineal gland of male Wistar rats upon aging. Under food restriction daily rhythmicity of serotonin 5-HT and 5-HTOH was abolished whereas NAS, 5-MIAA and NAT showed a significant decrease in their daily pulses upon food restriction in 3 months (m) old rats. Under forced day time feeding schedule the mean 24 h levels of serotonin have significantly decreased in 12 and 24 m old animals in SCN and pineal gland. Most of the serotonin metabolites in the SCN and pineal gland of 12 and 24 m old ad libitum fed group rats have shown rhythmicity. 5-HT, NAS, MEL and NAT have shown daily rhythm in the SCN of 12 and 24 m old rats whereas 5-MIAA and 5-MTOH did not show daily rhythm in both the age groups. The mean 24 h levels of 5-HTP, 5-HIAA, 5-MIAA, 5-MTOH, MEL and NAT were increased in the pineal gland of 12 and 24 months old rats. This work help demonstrate the role of TRF in synchronising age induced desynchronization in serotonin metabolome. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
3. Adenosine protects D-galactose induced alterations in rat model of aging via attenuating neurochemical profile and redox status.
- Author
-
Samad, Noreen, Nasir, Arooj, Rehman, Muhammad Habib ur, Bhatti, Sheraz Ahmed, and Imran, Imran
- Subjects
- *
GALACTOSE , *SEROTONIN , *ADENOSINES , *ANIMAL disease models , *BEHAVIORAL assessment , *LEARNING in animals , *MEMORY disorders - Abstract
Aging is the process that every organism faces. The aging model of brain has been developed by the use of d-galactose (d-Gal). Adenosine (Ad) being a neuroprotective agent that has been utilized in treatment of various neurological disorders. The aim of current study is to evaluate the outcome of Ad on d-Gal induced neurotoxicity which caused behavioral deficits, memory impairment and oxidative stress. Rats were treated with d-Gal at a dose of 300 mg/ml/kg and Ad 1 mg/ml/kg; intraperitoneally for 28 days. Behavioral assessment was performed after the treatment period. Animals were sacrificed after behavioral tests and their brains were collected, hippocampus were removed for biochemical and neurochemical analysis. The results showed that administration of Ad ameliorates the negative effects of d-Gal induced aging in various behavioral tests and increased the time spent in the open arm and light box in elevated plus maze (EPM) and light dark activity (LDA) tests respectively indicate anxiolytic effect; increased the mobility time in tail suspension test (TST) shows antidepressant effect; decreased escape latencies in Morris water maze (MWM) acquisition trials, increase entries and time spent in the target quadrant suggests improvement in learning ability of animals. Administration of Ad also decreased malondialdehyde (MDA) levels, increased antioxidant enzymes activity; decreased acetylcholinesterase (AChE) activity, increased 5-hydroxytryptamine (5-HT, serotonin) metabolism and normalized histopathological alteration in the hippocampus. It is concluded that anxiety, depression and memory impairment induced by d-Gal were protected by Ad through its antioxidant and neuro-modulatory effects. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
4. The modulatory role of serotonin-1A receptors of the basolateral amygdala and dorsal periaqueductal gray on the impact of hormonal variation on the conditioned fear response.
- Author
-
Sgobbi RF, Incrocci RM, Paliarin F, and Nobre MJ
- Subjects
- Animals, Female, Rats, Anxiety metabolism, Anxiety physiopathology, Conditioning, Classical physiology, Conditioning, Classical drug effects, Estrous Cycle physiology, Rats, Wistar, Serotonin metabolism, Basolateral Nuclear Complex metabolism, Basolateral Nuclear Complex drug effects, Estradiol pharmacology, Estradiol metabolism, Fear physiology, Fear drug effects, Periaqueductal Gray metabolism, Periaqueductal Gray drug effects, Progesterone pharmacology, Progesterone metabolism, Receptor, Serotonin, 5-HT1A metabolism, Reflex, Startle physiology, Reflex, Startle drug effects
- Abstract
Despite significant advances in the study of fear and fear memory formation, little is known about fear learning and expression in females. This omission has been proven surprising, as normal and pathological behaviors are highly influenced by ovarian hormones, particularly estradiol and progesterone. In the current study, we investigated the joint influence of serotonin (5-HT) neurotransmission and estrous cycle phases (low or high levels of estradiol and progesterone) on the expression of conditioned fear in a group of female rats that were previously divided according to their response to stressful stimuli into low or high anxiety-like subjects. The baseline amplitude of the unconditioned acoustic startle responses was high in high-anxiety female rats, with no effect on the estrous cycle observed. Data collected during the proestrus-estrus phase revealed that low-anxiety rats had startle amplitudes similar to those of high-anxiety rats. It is supposed that high-anxiety female rats benefit from increased estradiol and progesterone levels to achieve comparable potentiated startle amplitudes. In contrast, female rats experienced a significant decrease in hormone levels during the Diestrus phase. This decrease is believed to play a role in preventing them from displaying a heightened startle response when faced with strongly aversive stimuli. Data collected after 5-HT and 8-OH-DPAT were administered into the basolateral nuclei and dorsal periaqueductal gray suggest that 5-HT neurotransmission works with progesterone and estrogen to reduce startle potentiation, most likely by activating the serotonin-1A receptor subtype., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
5. Physical activity promotes brain development through serotonin during early childhood.
- Author
-
Jing JQ, Jia SJ, and Yang CJ
- Subjects
- Humans, Child, Preschool, Child, Animals, Serotonin metabolism, Brain growth & development, Brain metabolism, Brain physiology, Exercise physiology, Exercise psychology, Child Development physiology
- Abstract
Early childhood serves as a critical period for neural development and skill acquisition when children are extremely susceptible to the external environment and experience. As a crucial experiential stimulus, physical activity is believed to produce a series of positive effects on brain development, such as cognitive function, social-emotional abilities, and psychological well-being. The World Health Organization recommends that children engage in sufficient daily physical activity, which has already been strongly advocated in the practice of preschool education. However, the mechanisms by which physical activity promotes brain development are still unclear. The role of neurotransmitters, especially serotonin, in promoting brain development through physical activity has received increasing attention. Physical activity has been shown to stimulate the secretion of serotonin by increasing the bioavailability of free tryptophan and enriching the diversity of gut microbiota. Due to its important role in modulating neuronal proliferation, differentiation, synaptic morphogenesis, and synaptic transmission, serotonin can regulate children's explicit cognitive and social interaction behavior in the early stages of life. Therefore, we hypothesized that serotonin emerges as a pivotal transmitter that mediates the relationship between physical activity and brain development during early childhood. Further systematic reviews and meta-analyses are needed to specifically explore whether the type, intensity, dosage, duration, and degree of voluntariness of PA may affect the role of serotonin in the relationship between physical activity and brain function. This review not only helps us understand the impact of exercise on development but also provides a solid theoretical basis for increasing physical activity during early childhood., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
6. Genetic polymorphisms in the 5-HT and endocannabinoid systems moderate the association between childhood trauma and burnout in the general occupational population.
- Author
-
Li Y, Wang L, He Y, Zhu S, He SC, and Zhang XY
- Subjects
- Humans, Male, Female, Adult, Polymorphism, Single Nucleotide, Middle Aged, Burnout, Professional genetics, Burnout, Professional psychology, Serotonin metabolism, Serotonin genetics, Adverse Childhood Experiences psychology, Child Abuse psychology, Endocannabinoids genetics, Endocannabinoids metabolism, Serotonin Plasma Membrane Transport Proteins genetics, Amidohydrolases genetics, Receptor, Serotonin, 5-HT2A genetics
- Abstract
Background: Interactions between the serotonin (5-HT) and endocannabinoid (eCB) systems have been reported in the psychopathology of stress-related symptoms, while their interplay in regulating the relationship between childhood trauma and burnout remains unclear. In this study, we investigated the interaction of childhood trauma with genetic polymorphisms in these two systems in predicting burnout., Methods: Burnout, childhood trauma, and job stress were assessed using rating scales in 992 general occupational individuals. Genetic polymorphisms including HTR2A rs6313, 5-HTT rs6354 and FAAH rs324420, were genotyped. Linear hierarchical regression analysis and PROCESS macro in SPSS were used to examine two- and three-way interactions., Results: There were significant interactions of job stress × HTR2A rs6313 and childhood abuse × FAAH rs324420 on reduced personal accomplishment. Moreover, we found significant three-way interactions of childhood abuse × FAAH rs324420 × HTR2A rs6313 on cynicism and reduced personal accomplishment, childhood abuse × FAAH rs324420 × 5-HTT rs6354 on emotional exhaustion, and childhood neglect × FAAH rs324420 × 5-HTT rs6354 on reduced personal accomplishment. These results suggest that the FAAH rs324420 A allele carriers, when with some specific genetic polymorphisms of 5-HT system, would show more positive associations between childhood trauma and burnout., Conclusions: Genetic polymorphisms in the 5-HT and eCB systems may jointly moderate the impact of childhood trauma on burnout., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
7. Exploring the role of environmental enrichment and early life adversity on emotional development.
- Author
-
de Lima RMS, da Mata MJ, Santos JCPD, Costa L, Marques VHM, Bento LVDS, Lugon MDMV, Arcego DM, Barauna VG, Bittencourt AS, and Bittencourt APSV
- Subjects
- Anxiety psychology, Maternal Deprivation, Male, Female, Animals, Rats, Motor Activity, Exploratory Behavior, Memory, Dorsal Raphe Nucleus metabolism, Amygdala metabolism, Serotonin metabolism, Fear psychology, Adverse Childhood Experiences psychology, Environment, Emotions
- Abstract
Early life adversity has been linked with a higher probability of developing behavioral impairments and environmental manipulation is a strategy that may reduce the negative effects of exposure to adversity in early life. Here, we focused on exploring the influence of environmental enrichment (EE) as a protective factor in the context of early life adversity. We hypothesized that 24 hours of maternal deprivation (MD), in the second week of life, could induce anxiety-like behavior alterations and that exposure to EE could induce resilience to these behaviors due to alterations in the serotonergic system. Male Wistar rats were exposed to MD, on postnatal days 11 and 13, and to EE, after weaning. In adulthood, we performed a series of behavioral tests for fear, anxiety, and locomotor activity. We also measured the levels of serotonin in the amygdala and dorsal raphe nucleus. Our results revealed that MD does not impact fear behavior or the levels of serotonin, while EE decreases locomotor activity in a novel environment and enhances exploration in the predator odor test. EE also decreases serotonin in the amygdala and increases its turnover rate levels. Our findings provide insights into the critical timeframe during which stress exposure impacts the development and confirm that exposure to EE has an independent and protective effect for anxiety-like behaviors later in life., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
8. Navigating glioblastoma complexity: the interplay of neurotransmitters and chromatin.
- Author
-
Romero-Reyes J, Vázquez-Martínez ER, Silva CC, Molina-Hernández A, Díaz NF, and Camacho-Arroyo I
- Subjects
- Humans, Epigenesis, Genetic, Dopamine metabolism, Animals, Serotonin metabolism, Gene Expression Regulation, Neoplastic, Glioblastoma metabolism, Glioblastoma genetics, Glioblastoma pathology, Neurotransmitter Agents metabolism, Chromatin metabolism, Brain Neoplasms metabolism, Brain Neoplasms genetics, Brain Neoplasms pathology, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells pathology, Tumor Microenvironment genetics
- Abstract
Glioblastoma is the most aggressive brain cancer with an unfavorable prognosis for patient survival. Glioma stem cells, a subpopulation of cancer cells, drive tumor initiation, self-renewal, and resistance to therapy and, together with the microenvironment, play a crucial role in glioblastoma maintenance and progression. Neurotransmitters such as noradrenaline, dopamine, and serotonin have contrasting effects on glioblastoma development, stimulating or inhibiting its progression depending on the cellular context and through their action on glioma stem cells, perhaps changing the epigenetic landscape. Recent studies have revealed that serotonin and dopamine induce chromatin modifications related to transcriptional plasticity in the mammalian brain and possibly in glioblastoma; however, this topic still needs to be explored because of its potential implications for glioblastoma treatment. Also, it is essential to consider that neurotransmitters' effects depend on the tumor's microenvironment since it can significantly influence the response and behavior of cancer cells. This review examines the possible role of neurotransmitters as regulators of glioblastoma development, focusing on their impact on the chromatin of glioma stem cells., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
9. Passively administered fluoxetine reaches the juvenile brain of FSL rats and reduces antioxidant defences, without altering serotonin turnover.
- Author
-
Steyn SF, Rheeders M, Viljoen FP, and Brand L
- Subjects
- Animals, Female, Rats, Antioxidants metabolism, Antioxidants pharmacology, Male, Pregnancy, Glutathione metabolism, Fluoxetine analogs & derivatives, Fluoxetine pharmacology, Serotonin metabolism, Brain metabolism, Brain drug effects, Selective Serotonin Reuptake Inhibitors administration & dosage, Selective Serotonin Reuptake Inhibitors pharmacology
- Abstract
Background: Fluoxetine is present in breast milk, yet it is unclear to what extent it, or its active metabolite, norfluoxetine, reaches the brain of the infant and what the effects of such exposure on neurobiological processes are. We therefore aimed to quantify the concentration of passively administered fluoxetine and norfluoxetine in the whole brains of exposed Flinders sensitive line (FSL) offspring and establish their influence on serotonergic function and redox status., Methods: Adult FSL dams received fluoxetine (10 mg/kg/day), or placebo for fourteen days, beginning on postpartum day 04. Offspring were passively exposed to fluoxetine until postnatal day 18 and euthanized on postnatal day 22. Whole brain fluoxetine, norfluoxetine, serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and reduced (GSH) and oxidized glutathione (GSSG) concentrations were measured via liquid chromatography-mass spectrometry (LC-MS) analysis., Results: Whole-brain serotonin and 5-hydroxyindoleacetic acid concentrations, and serotonin turnover (5-HIAA/5-HT) were comparable between strains. Treatment-naïve FSL rats had lower GSH and higher GSSG whole-brain concentrations, relative to FRL controls, and an overall decreased GSH/GSSG ratio. Passively administered fluoxetine resulted in undetectable whole-brain concentrations, while norfluoxetine averaged 41.28 ± 6.47 ng/g. Serotonin turnover of FSL rats was unaffected by passively administered fluoxetine, while redox status (GSH/GSSG) was decreased., Conclusion: Our findings confirm that passively administered fluoxetine reaches the infant brain in the form of norfluoxetine and may manipulate processes of oxidative stress regulation. Further studies into the long-term bio-behavioural effects are however needed to effectively inform breast feeding mothers on the safety of antidepressant-use., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
10. Role of the circadian nuclear receptor REV-ERBα in dorsal raphe serotonin synthesis in mood regulation.
- Author
-
Park I, Choi M, Kim J, Jang S, Kim D, Kim J, Choe Y, Geum D, Yu SW, Choi JW, Moon C, Choe HK, Son GH, and Kim K
- Subjects
- Animals, Mice, Male, Affect physiology, Mice, Knockout, Mice, Inbred C57BL, Transcription Factors metabolism, Transcription Factors genetics, Depression metabolism, Nuclear Receptor Subfamily 1, Group D, Member 1 metabolism, Nuclear Receptor Subfamily 1, Group D, Member 1 genetics, Dorsal Raphe Nucleus metabolism, Serotonin metabolism, Serotonin biosynthesis, Tryptophan Hydroxylase metabolism, Tryptophan Hydroxylase genetics, Circadian Rhythm
- Abstract
Affective disorders are frequently associated with disrupted circadian rhythms. The existence of rhythmic secretion of central serotonin (5-hydroxytryptamine, 5-HT) pattern has been reported; however, the functional mechanism underlying the circadian control of 5-HTergic mood regulation remains largely unknown. Here, we investigate the role of the circadian nuclear receptor REV-ERBα in regulating tryptophan hydroxylase 2 (Tph2), the rate-limiting enzyme of 5-HT synthesis. We demonstrate that the REV-ERBα expressed in dorsal raphe (DR) 5-HTergic neurons functionally competes with PET-1-a nuclear activator crucial for 5-HTergic neuron development. In mice, genetic ablation of DR 5-HTergic REV-ERBα increases Tph2 expression, leading to elevated DR 5-HT levels and reduced depression-like behaviors at dusk. Further, pharmacological manipulation of the mice DR REV-ERBα activity increases DR 5-HT levels and affects despair-related behaviors. Our findings provide valuable insights into the molecular and cellular link between the circadian rhythm and the mood-controlling DR 5-HTergic systems., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
11. Long-Term Impact of Early-Life Stress on Serotonin Connectivity.
- Author
-
Ramkumar R, Edge-Partington M, Terstege DJ, Adigun K, Ren Y, Khan NS, Rouhi N, Jamani NF, Tsutsui M, Epp JR, and Sargin D
- Subjects
- Animals, Female, Male, Mice, Prefrontal Cortex metabolism, Prefrontal Cortex physiopathology, Mice, Inbred C57BL, Disease Models, Animal, Optogenetics, Anxiety physiopathology, Anxiety metabolism, Neural Pathways physiopathology, Proto-Oncogene Proteins c-fos metabolism, Behavior, Animal physiology, Stress, Psychological metabolism, Stress, Psychological physiopathology, Serotonin metabolism, Raphe Nuclei metabolism
- Abstract
Background: Chronic childhood stress is a prominent risk factor for developing affective disorders, yet mechanisms underlying this association remain unclear. Maintenance of optimal serotonin (5-HT) levels during early postnatal development is critical for the maturation of brain circuits. Understanding the long-lasting effects of early-life stress (ELS) on serotonin-modulated brain connectivity is crucial to develop treatments for affective disorders arising from childhood stress., Methods: Using a mouse model of chronic developmental stress, we determined the long-lasting consequences of ELS on 5-HT circuits and behavior in females and males. Using FosTRAP mice, we cross-correlated regional c-Fos density to determine brain-wide functional connectivity of the raphe nucleus. We next performed in vivo fiber photometry to establish ELS-induced deficits in 5-HT dynamics and optogenetics to stimulate 5-HT release to improve behavior., Results: Adult female and male mice exposed to ELS showed heightened anxiety-like behavior. ELS further enhanced susceptibility to acute stress by disrupting the brain-wide functional connectivity of the raphe nucleus and the activity of 5-HT neuron population, in conjunction with increased orbitofrontal cortex (OFC) activity and disrupted 5-HT release in medial OFC. Optogenetic stimulation of 5-HT terminals in the medial OFC elicited an anxiolytic effect in ELS mice in a sex-dependent manner., Conclusions: These findings suggest a significant disruption in 5-HT-modulated brain connectivity in response to ELS, with implications for sex-dependent vulnerability. The anxiolytic effect of the raphe-medial OFC circuit stimulation has potential implications for developing targeted stimulation-based treatments for affective disorders that arise from early life adversities., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
12. Lycopene alleviates BCG-induced depressive phenotypes in mice by disrupting 5-HT3 receptor - IDO1 interplay in the brain.
- Author
-
Deore R, Ansari R, Awathale SN, Shelke M, Badwaik HR, Goyal SN, and Nakhate KT
- Subjects
- Animals, Mice, Male, Phenotype, Molecular Docking Simulation, Serotonin metabolism, BCG Vaccine pharmacology, Ondansetron pharmacology, Behavior, Animal drug effects, Serotonin 5-HT3 Receptor Antagonists pharmacology, Antidepressive Agents pharmacology, Minocycline pharmacology, Lycopene pharmacology, Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism, Indoleamine-Pyrrole 2,3,-Dioxygenase antagonists & inhibitors, Depression drug therapy, Depression metabolism, Brain drug effects, Brain metabolism, Receptors, Serotonin, 5-HT3 metabolism
- Abstract
The 5-HT3 receptor and indoleamine 2,3-dioxygenase 1 (IDO1) enzyme play a crucial role in the pathogenesis of depression as their activation reduces serotonin contents in the brain. Since molecular docking analysis revealed lycopene as a potent 5-HT3 receptor antagonist and IDO1 inhibitor, we hypothesized that lycopene might disrupt the interplay between the 5-HT3 receptor and IDO1 to mitigate depression. In mice, the depression-like phenotypes were induced by inoculating Bacillus Calmette-Guerin (BCG). Lycopene (intraperitoneal; i.p.) was administered alone or in combination with 5-HT3 receptor antagonist ondansetron (i.p.) or IDO1 inhibitor minocycline (i.p.), and the behavioral screening was performed by the sucrose preference test, open field test, tail suspension test, and splash test which are based on the different principles. Further, the brains were subjected to the biochemical analysis of serotonin and its precursor tryptophan by the HPLC. The results showed depression-like behavior in BCG-inoculated mice, which was reversed by lycopene administration. Moreover, prior treatment with ondansetron or minocycline potentiated the antidepressant action of lycopene. Minocycline pretreatment also enhanced the antidepressant effect of ondansetron indicating the regulation of IDO1 activity by 5-HT3 receptor-triggered signaling. Biochemical analysis of brain samples revealed a drastic reduction in the levels of tryptophan and serotonin in depressed animals, which were restored following treatment with lycopene and its combination with ondansetron or minocycline. Taken together, the data from molecular docking, behavioral experiments, and biochemical estimation suggest that lycopene might block the 5-HT3 receptor and consequently inhibit the activity of IDO1 to ameliorate BCG-induced depression in mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
13. Vocal and tongue exercise in early to mid-stage Parkinson disease using the Pink1-/- rat.
- Author
-
Hoffmeister JD, Broadfoot CK, Schaen-Heacock NE, Lechner SA, Krasko MN, Nisbet AF, Russell J, Szot J, Glass TJ, Connor NP, Kelm-Nelson CA, and Ciucci MR
- Subjects
- Animals, Male, Protein Kinases metabolism, Protein Kinases genetics, Rats, Physical Conditioning, Animal physiology, Physical Conditioning, Animal methods, Serotonin metabolism, Rats, Transgenic, Tongue physiopathology, Parkinson Disease physiopathology, Disease Models, Animal, Vocalization, Animal physiology
- Abstract
Vocal and swallowing deficits are common in Parkinson disease (PD). Because these impairments are resistant to dopamine replacement therapies, vocal and lingual exercise are the primary treatment, but not all individuals respond to exercise and neural mechanisms of treatment response are unclear. To explore putative mechanisms, we used the progressive Pink1-/- rat model of early to mid-stage PD and employed vocal and lingual exercises at 6- and 10-months of age in male Pink1-/- and wild type (WT) rats. We hypothesized that vocal and lingual exercise would improve vocal and tongue use dynamics and increase serotonin (5HT) immunoreactivity in related brainstem nuclei. Rats were tested at baseline and after 8 weeks of exercise or sham exercise. At early-stage PD (6 months), vocal exercise resulted in increased call complexity, but did not change intensity, while at mid-stage (10 months), vocal exercise no longer influenced vocalization complexity. Lingual exercise increased tongue force generation and reduced relative optical density of 5HT in the hypoglossal nucleus at both time points. The effects of vocal and lingual exercise at these time points are less robust than in prodromal stages observed in previous work, suggesting that early exercise interventions may yield greater benefit. Future work targeting optimization of exercise at later time points may facilitate clinical translation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
14. Lysergic acid diethylamide induces behavioral changes in Caenorhabditis elegans.
- Author
-
Ornelas IM, Carrilho BS, Ventura MAVC, Domith I, de V Silveira CM, Dos Santos VF, Delou JM, Moll F, Pereira HMG, Junqueira M, Aguilaniu H, and Rehen S
- Subjects
- Animals, Locomotion drug effects, Receptors, Serotonin drug effects, Receptors, Serotonin metabolism, Behavior, Animal drug effects, Caenorhabditis elegans Proteins metabolism, Serotonin metabolism, Caenorhabditis elegans drug effects, Lysergic Acid Diethylamide pharmacology, Hallucinogens pharmacology
- Abstract
Lysergic acid diethylamide (LSD) is a synthetic psychedelic compound with potential therapeutic value for psychiatric disorders. This study aims to establish Caenorhabditis elegans as an in vivo model for examining LSD's effects on locomotor behavior. Our results demonstrate that LSD is absorbed by C. elegans and that the acute treatment reduces animal speed, similar to the role of endogenous serotonin. This response is mediated in part by the serotonergic receptors SER-1 and SER-4. Our findings highlight the potential of this nematode as a new experimental model in psychedelic research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
15. Direct serotonin release in humans shapes aversive learning and inhibition.
- Author
-
Colwell MJ, Tagomori H, Shang F, Cheng HI, Wigg CE, Browning M, Cowen PJ, Murphy SE, and Harmer CJ
- Subjects
- Humans, Male, Female, Adult, Young Adult, Reinforcement, Psychology, Avoidance Learning drug effects, Avoidance Learning physiology, Emotions physiology, Inhibition, Psychological, Selective Serotonin Reuptake Inhibitors pharmacology, Learning physiology, Decision Making physiology, Memory physiology, Memory drug effects, Serotonin metabolism
- Abstract
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., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
16. Brain region-specific action of ketamine as a rapid antidepressant.
- Author
-
Chen M, Ma S, Liu H, Dong Y, Tang J, Ni Z, Tan Y, Duan C, Li H, Huang H, Li Y, Cao X, Lingle CJ, Yang Y, and Hu H
- Subjects
- Animals, Male, Mice, Brain-Derived Neurotrophic Factor metabolism, Brain-Derived Neurotrophic Factor genetics, Hippocampus drug effects, Hippocampus metabolism, Mice, Inbred C57BL, Mice, Knockout, Pyramidal Cells drug effects, Pyramidal Cells metabolism, Serotonin metabolism, Antidepressive Agents pharmacology, Depression drug therapy, Depression metabolism, Habenula drug effects, Habenula metabolism, Ketamine pharmacology, Ketamine administration & dosage, Receptors, N-Methyl-D-Aspartate antagonists & inhibitors, Receptors, N-Methyl-D-Aspartate genetics
- Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
17. Agouti-Induced Anxiety-Like Behavior Is Mediated by Central Serotonergic Pathways in Zebrafish.
- Author
-
Godino-Gimeno A, Rocha A, Chivite M, Saera-Vila A, Rotllant J, Míguez JM, and Cerdá-Reverter JM
- Subjects
- Animals, Male, Female, Animals, Genetically Modified, Behavior, Animal drug effects, Behavior, Animal physiology, Zebrafish Proteins genetics, Zebrafish Proteins metabolism, Fluoxetine pharmacology, Selective Serotonin Reuptake Inhibitors pharmacology, Dopamine metabolism, Agouti-Related Protein metabolism, Agouti-Related Protein genetics, Zebrafish, Anxiety metabolism, Anxiety psychology, Serotonin metabolism
- Abstract
Overexpression of the agouti-signaling protein ( asip1 ), an endogenous melanocortin antagonist, under the control of a constitutive promoter in zebrafish [Tg(Xla.Eef1a1:Cau.Asip1]iim4] ( asip1 -Tg) increases food intake by reducing sensitivity of the central satiety systems and abolish circadian activity rhythms. The phenotype also shows increased linear growth and body weight, yet no enhanced aggressiveness in dyadic fights is observed. In fact, asip1 -Tg animals choose to flee to safer areas rather than face a potential threat, thus suggesting a potential anxiety-like behavior (ALB). Standard behavioral tests, i.e., the open field test (OFT), the novel object test (NOT), and the novel tank dive test (NTDT), were used to investigate thigmotaxis and ALB in male and female zebrafish. Results showed that the asip1 -Tg strain exhibited severe ALB in every test, mainly characterized by pronounced freezing behavior and increased linear and angular swimming velocities. asip1 -Tg animals exhibited low central serotonin (5-HT) and dopamine (DA) levels and high turnover rates, thus suggesting that central monoaminergic pathways might mediate melanocortin antagonist-induced ALB. Accordingly, the treatment of asip1 -Tg animals with fluoxetine, a selective serotonin reuptake inhibitor (SSRI), reversed the ALB phenotype in NTDT as well as 5-HT turnover. Genomic and anatomical data further supported neuronal interaction between melanocortinergic and serotonergic systems. These results suggest that inhibition of the melanocortin system by ubiquitous overexpression of endogenous antagonist has an anxiogenic effect mediated by serotonergic transmission., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)
- Published
- 2024
- Full Text
- View/download PDF
18. Tongbian formula alleviates slow transit constipation by increasing intestinal butyric acid to activate the 5-HT signaling.
- Author
-
Li D, Si X, Hua Y, Qian Y, Li H, Lv N, Fang Q, Han X, and Xu T
- Subjects
- Animals, Rats, Male, Rats, Sprague-Dawley, Gastrointestinal Transit drug effects, Loperamide, Disease Models, Animal, Colon metabolism, Colon drug effects, Constipation drug therapy, Constipation metabolism, Butyric Acid pharmacology, Signal Transduction drug effects, Drugs, Chinese Herbal pharmacology, Gastrointestinal Microbiome drug effects, Serotonin metabolism
- Abstract
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., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
19. Effects of rumen-protected 5-hydroxytryptophan on circulating serotonin concentration, behaviour, and mammary gland involution in goats.
- Author
-
Chen J, Huang G, Wei B, Yue S, Chang X, Han S, Dong X, Zhao Y, Zhang X, Zhao Z, Dong G, and Sun Y
- Subjects
- Animals, Female, Behavior, Animal drug effects, Dietary Supplements analysis, Milk chemistry, Milk metabolism, Diet veterinary, Goats physiology, 5-Hydroxytryptophan pharmacology, 5-Hydroxytryptophan administration & dosage, Rumen metabolism, Rumen drug effects, Serotonin blood, Serotonin metabolism, Mammary Glands, Animal drug effects, Lactation drug effects
- Abstract
The risk of acquiring new intramammary infections is high at the end of lactation, especially for the high milk-producing dairy animals. Resistance to bacterial infection increases following the completion of mammary gland involution after milking cessation. The serotonin precursor 5-hydroxytryptophan (5-HTP) could accelerate involution by increasing circulating serotonin levels, but ruminal microbes may degrade 5-HTP if orally administered to adult ruminants. It is unclear whether rumen-protected 5-HTP could effectively mediate circulating serotonin (5-hydroxytryptamine, 5-HT) and therefore accelerate mammary gland involution in ruminants. Goats were used as a model in the current study to investigate the effects of rumen-protected 5-HTP on behaviour, 5-HT metabolism, and mammary involution in ruminants. In the first experiment, 16 female Dazu black goats were assigned to one of four groups in a randomised block design. The treatments included a basal diet plus 0, 4, 20, or 100 mg/kg BW of rumen-protected 5-HTP. Serum was collected at 0, 3, 6, 12, and 24 h after offering the rumen-protected 5-HTP in the morning feed, and the behaviours were monitored. In the second experiment, 12 female Dazu black goats (Somatic cell count < 250 000) were randomly assigned to the control (basal diet) or rumen-protected 5-HTP group (basal diet plus 20 mg/kg BW). Milk or mammary secretions were manually collected aseptically on d -1, 1, 2, 3, 4, and 5 around weaning. The results depicted that rumen-protected 5-HTP supplementation elevated circulating 5-HTP and 5-hydroxyindole acetic acid concentrations, while 20 mg/kg BW of rumen-protected 5-HTP supplementation lowered the goats' locomotive activity. A high concentration of rumen-protected 5-HTP (100 mg/kg BW) increased serum alkaline phosphatase and gamma-glutamyl transpeptidase concentrations. Moreover, oral supplementation with 20 mg/kg BW of rumen-protected 5-HTP accelerated mammary gland involution and reduced feed intake in goats after weaning. These results demonstrate that oral supplementation with rumen-protected 5-HTP influences 5-HT metabolism and accelerates mammary gland involution after milking cessation in ruminants., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
20. New evidence linking serotonin and memory.
- Author
-
Le Bras A
- Subjects
- Animals, Mice, Serotonin metabolism, Memory drug effects
- Published
- 2024
- Full Text
- View/download PDF
21. Morphometric analysis and functional insights into the serotonergic system of Girardia tigrina (Tricladida, Platyhelminthes).
- Author
-
Kreshchenko ND and Ermakov AM
- Subjects
- Animals, Tryptophan Hydroxylase metabolism, Tryptophan Hydroxylase genetics, Platyhelminths, Serotonergic Neurons metabolism, Serotonin Plasma Membrane Transport Proteins metabolism, Serotonin Plasma Membrane Transport Proteins genetics, Serotonin metabolism, Planarians anatomy & histology, Planarians physiology
- Abstract
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., (© 2024 Wiley Periodicals LLC.)- Published
- 2024
- Full Text
- View/download PDF
22. Adaptation to photoperiod via dynamic neurotransmitter segregation.
- Author
-
Maddaloni G, Chang YJ, Senft RA, and Dymecki SM
- Subjects
- Animals, Female, Mice, Amino Acid Transport Systems, Acidic deficiency, Amino Acid Transport Systems, Acidic genetics, Amino Acid Transport Systems, Acidic metabolism, CLOCK Proteins genetics, Darkness, Dorsal Raphe Nucleus cytology, Dorsal Raphe Nucleus metabolism, Neural Pathways physiology, Preoptic Area cytology, Preoptic Area metabolism, Presynaptic Terminals metabolism, Presynaptic Terminals physiology, Rabies virus, Serotonin metabolism, Sleep physiology, Wakefulness physiology, Adaptation, Physiological physiology, Axons metabolism, Axons physiology, Circadian Rhythm physiology, Neurotransmitter Agents metabolism, Photoperiod
- Abstract
Changes in the amount of daylight (photoperiod) alter physiology and behaviour
1,2 . Adaptive responses to seasonal photoperiods are vital to all organisms-dysregulation associates with disease, including affective disorders3 and metabolic syndromes4 . The circadian rhythm circuitry is implicated in such responses5,6 , yet little is known about the precise cellular substrates that underlie phase synchronization to photoperiod change. Here we identify a brain circuit and system of axon branch-specific and reversible neurotransmitter deployment that are critical for behavioural and sleep adaptation to photoperiod. A type of neuron called mrEn1-Pet17 in the mouse brainstem median raphe nucleus segregates serotonin from VGLUT3 (also known as SLC17A8, a proxy for glutamate) to different axonal branches that innervate specific brain regions involved in circadian rhythm and sleep-wake timing8,9 . This branch-specific neurotransmitter deployment did not distinguish between daylight and dark phase; however, it reorganized with change in photoperiod. Axonal boutons, but not cell soma, changed neurochemical phenotype upon a shift away from equinox light/dark conditions, and these changes were reversed upon return to equinox conditions. When we genetically disabled Vglut3 in mrEn1-Pet1 neurons, sleep-wake periods, voluntary activity and clock gene expression did not synchronize to the new photoperiod or were delayed. Combining intersectional rabies virus tracing and projection-specific neuronal silencing, we delineated a preoptic area-to-mrEn1Pet1 connection that was responsible for decoding the photoperiodic inputs, driving the neurotransmitter reorganization and promoting behavioural synchronization. Our results reveal a brain circuit and periodic, branch-specific neurotransmitter deployment that regulates organismal adaptation to photoperiod change., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2024
- Full Text
- View/download PDF
23. Modified Zhizhu Pill improves the loperamide-induced slow transit constipation via gut microbiota and neurotransmitters in microbiota-gut-brain axis.
- Author
-
Shen XL, Zhou XT, Ren M, Shi X, Zhang HZ, Wang Y, and Yang M
- Subjects
- Animals, Rats, Male, Brain-Gut Axis drug effects, Neurotransmitter Agents metabolism, Gastrointestinal Transit drug effects, Antidiarrheals pharmacology, Disease Models, Animal, Serotonin metabolism, Serotonin blood, Dysbiosis drug therapy, Loperamide, Constipation drug therapy, Gastrointestinal Microbiome drug effects, Rats, Sprague-Dawley, Drugs, Chinese Herbal pharmacology, Drugs, Chinese Herbal therapeutic use
- Abstract
Background: Slow-transmission constipation is a type of intractable constipation with unknown etiology and unclear pathogenesis., Objective: The intention of this study was to evaluate the therapeutic effect and possible mechanism of Modified Zhizhu Pills on loperamide-induced slow transit constipation., Methods: The effects of the Modified Zhizhu Pill were evaluated in a rat model of constipation induced by subcutaneous administration of loperamide. Fecal parameters (fecal count, fecal water content, and fecal hardness) were measured in constipated rats. The substance, target, and pathway basis of the Modified Zhizhu Pill on constipation was investigated using network pharmacology. The microflora in rats was determined. Serum neurotransmitters (acetylcholine and 5-hydroxytryptamine) were measured in rats and their relationship with the gut microbiota was assessed., Results: Modified Zhizhu Pill increased the number of bowel movements and fecal water content, and decreased fecal hardness and transit time. Network pharmacological analysis showed that Modified Zhizhu Pill can target multiple constipation-related targets and pathways through multiple potential active ingredients. Modified Zhizhu Pill alleviated loperamide-induced microbiota dysbiosis. Modified Zhizhu Pill increased serum 5-hydroxytryptamine and acetylcholine. The increase in serum 5-hydroxytryptamine and acetylcholine was associated with rat gut microbiota., Conclusion: These results suggest that Modified Zhizhu Pill may increase intestinal motility and ultimately relieve constipation by improving microecological dysbiosis and neurotransmission., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
24. Patients with uncontrolled hypertension subjected to cardiopulmonary bypass have altered coronary vasomotor responses to serotonin.
- Author
-
Harris DD, Li J, Sabe SA, Banerjee D, Pearson E, Nho JW, Ehsan A, Sodha N, Feng J, and Sellke FW
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Arterioles metabolism, Arterioles physiopathology, Arterioles drug effects, Heart Arrest, Induced adverse effects, Vasoconstriction drug effects, Receptors, Serotonin metabolism, Vasodilation drug effects, Cardiopulmonary Bypass adverse effects, Serotonin metabolism, Serotonin pharmacology, Hypertension physiopathology, Hypertension metabolism, Hypertension etiology, Coronary Vessels physiopathology
- Abstract
Background: We previously found that cardioplegic arrest and cardiopulmonary bypass are associated with altered coronary arteriolar response to serotonin in patients undergoing cardiac surgery. In this study, we investigated the effects of hypertension on coronary microvascular vasomotor tone in response to serotonin and alterations in serotonin receptor protein expression in the setting of cardioplegic arrest and cardiopulmonary bypass., Methods: Coronary arterioles were dissected from harvested pre- and post-cardioplegic arrest and cardiopulmonary bypass right atrial tissue samples of patients undergoing cardiac surgery with normotension, well-controlled hypertension, and uncontrolled hypertension. Vasomotor tone was assessed by video-myography, and protein expression was measured with immunoblotting., Results: Pre-cardioplegic arrest and cardiopulmonary bypass, serotonin induced moderate relaxation responses of coronary arterioles in normotension and well-controlled hypertension patients, whereas serotonin caused moderate contractile responses in uncontrolled hypertension patients. Post-cardioplegic arrest and cardiopulmonary bypass, serotonin caused contractile responses of coronary arterioles in all 3 groups. The post-cardioplegic arrest and cardiopulmonary bypass contractile response to serotonin was significantly higher in the uncontrolled hypertension group compared with the normotension or well-controlled hypertension groups (P < .05). Pre-cardioplegic arrest and cardiopulmonary bypass, expression of the serotonin 1A receptor was significantly lower in the uncontrolled hypertension group compared with the well-controlled hypertension and normotension groups (P = .01 and P < .001). Serotonin 1B receptor expression was higher in the uncontrolled hypertension group compared with the normotension or well-controlled hypertension groups post-cardioplegic arrest and cardiopulmonary bypass (P = .03 and P = .046)., Conclusion: Uncontrolled hypertension is associated with an increased coronary contractile response of coronary microvessels to serotonin and altered serotonin receptor protein expression after cardioplegic arrest and cardiopulmonary bypass. These findings may contribute to a worse postoperative coronary spasm and worsened recovery of coronary perfusion in patients with uncontrolled hypertension after cardioplegic arrest and cardiopulmonary bypass and cardiac surgery., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
25. Intestinal barrier function in the naked mole-rat: an emergent model for gastrointestinal insights.
- Author
-
Aguilera-Lizarraga J, Ritoux A, Bulmer DC, and Smith ESJ
- Subjects
- Animals, Mice, Male, Goblet Cells metabolism, Goblet Cells drug effects, Capsaicin pharmacology, Bradykinin pharmacology, Bradykinin metabolism, Serotonin metabolism, Mice, Inbred C57BL, Intestinal Barrier Function, Mole Rats, Intestinal Mucosa metabolism, Intestinal Mucosa drug effects, Permeability
- Abstract
The intestinal barrier plays a crucial role in homeostasis by both facilitating the absorption of nutrients and fluids and providing a tight shield to prevent the invasion by either pathogen or commensal microorganisms. Intestinal barrier malfunction is associated with systemic inflammation, oxidative stress, and decreased insulin sensitivity, which may lead to the dysregulation of other tissues. Therefore, a deeper understanding of physiological aspects related to an enhanced barrier function is of significant scientific and clinical relevance. The naked mole-rat has many unusual biological features, including attenuated colonic neuron sensitivity to acid and bradykinin and resistance to chemical-induced intestinal damage. However, insight into their intestinal barrier physiology is scarce. Here, we observed notable macroscopic and microscopic differences in intestinal tissue structure between naked mole-rats and mice. Moreover, naked mole-rats showed increased number of larger goblet cells and elevated mucus content. In measuring gut permeability, naked mole-rats showed reduced permeability compared with mice, measured as transepithelial electrical resistance, especially in ileum. Furthermore, intestinal ion secretion induced by serotonin, bradykinin, histamine, and capsaicin was significantly reduced in naked mole-rats compared with mice, despite the expression of receptors for all these agonists. In addition, naked mole-rats exhibited reduced prosecretory responses to the nonselective adenylate cyclase activator forskolin. Collectively, these findings indicate that naked mole-rats possess a robust and hard-to-penetrate gastrointestinal barrier that is resistant to environmental and endogenous irritants. Naked mole-rats may therefore provide valuable insights into the physiology of the intestinal barrier and set the stage for the development of innovative and effective therapies. NEW & NOTEWORTHY This is the first study to characterize the intestinal function of naked mole-rats. We found that these animals show a robust gut tissue structure, displaying thicker intestinal layers, longer villi, and larger crypts. Naked mole-rats showed more and larger goblet cells, with increased mucus content. Intestinal permeability, especially in the ileum, was substantially lower than that of mice. Finally, naked mole-rats showed reduced intestinal anion secretion in response to serotonin, bradykinin, histamine, capsaicin, and forskolin.
- Published
- 2024
- Full Text
- View/download PDF
26. A Novel Herbal Composition Alleviates Functional Constipation, Reduces Gastrointestinal Transit Time, and Improves Bowel Function in Adults: A Double-Blind, Randomized Clinical Study.
- Author
-
Singh G, Dixit I, Kalman D, and Gogineni NT
- Subjects
- Humans, Female, Male, Double-Blind Method, Adult, Middle Aged, Gastrins blood, Defecation drug effects, Hydrocortisone blood, Serotonin blood, Serotonin metabolism, Treatment Outcome, Dietary Supplements, Interleukin-10 blood, Interleukin-6 blood, Constipation drug therapy, Plant Extracts therapeutic use, Plant Extracts pharmacology, Plant Extracts administration & dosage, Gastrointestinal Transit drug effects, Quality of Life
- Abstract
Background and Objective: A recent proof-of-concept pilot clinical study has demonstrated that consumption of CL18100F4, a proprietary herbal blend of Withania somnifera root and Abelmoschus esculentus fruit extracts, significantly relieved the participants from functional constipation and improved their quality of life. The objective of the present randomized, double-blind, placebo-controlled study was to reevaluate the efficacy and tolerability of CL18100F4 in a larger number of subjects., Methods: Male and female subjects ( n = 135; age: 25-60 years), selected through Rome-IV criteria for functional constipation, were randomized into placebo and 300 or 500 mg of CL18100F4 groups and supplemented daily over 60 consecutive days. The primary efficacy outcome measure was Patient Assessment of Constipation-Symptoms (PAC-SYM), evaluated at baseline and on days 7, 30, and 60 of supplementation. The secondary efficacy parameters included Patient Assessment of Constipation-Quality of Life (PAC-QOL), Gastrointestinal Symptom Rating Scale (GSRS) scores, Gastrointestinal Transit Time (GIT), and Complete Spontaneous Bowel Movement (CSBM). Serum levels of Interleukin (IL)-6, IL-10, cortisol, gastrin, serotonin, Diamine oxidase (DAO), and Zonulin were measured., Results: CL18100F4 supplementation significantly ( p < 0.001) reduced the PAC-SYM, PAC-QOL, GSRS scores, and GIT and improved CSBM scores. CL18100F4 significantly improved ( p < 0.001) sleep quality and decreased depression and anxiety symptoms in the participants. Notably, relief in constipation symptoms and improved gastrointestinal (GI) function were reported starting from day 7. Furthermore, CL18100F4 supplementation significantly ( p < 0.001) increased the serum levels of IL-10, DAO, serotonin, gastrin, reduced IL-6, cortisol, and Zonulin. No major adverse events were observed. Participants' vital signs, hematology, clinical biochemistry, and urinalysis parameters were within the normal ranges., Conclusion: The present investigation demonstrates that CL18100F4 is tolerable and efficacious in relieving functional constipation, alleviating GI dysfunction, and improving associated non-GI factors in male and female adults.
- Published
- 2024
- Full Text
- View/download PDF
27. Analysis of Natural Antibodies during the Development of Phantom Pain Syndrome.
- Author
-
Myagkova MA, Petrochenko SN, Bobrova ZV, and Orlova EA
- Subjects
- Humans, Male, Female, beta-Endorphin, Middle Aged, Antibodies immunology, Adult, Histamine immunology, Histamine metabolism, Angiotensins immunology, Serotonin metabolism, Serotonin immunology, Phantom Limb physiopathology, Phantom Limb immunology
- Abstract
We determined natural antibodies (n-Abs) to the regulators of the main systems of biochemical homeostasis: β-endorphin, serotonin, dopamine, histamine, orphanin, angiotensin, GABA, glutamate, bradykinin, vasopressin, thrombin, and α-2-macroglobulin in individuals with phantom pain syndrome (PPS), resulting from amputation after injury. It was established that each patient has an individual immunoprofile, but for all of them there was a significant increase in the level of antibodies to serotonin, histamine, and angiotensin, which reflect the chronicity of the pain syndrome and do not depend on the self-assessment of the severity of PPS. Determination of the role of regulators of biochemical homeostasis in the development of phantom pain showed that, at high, moderate, and weak severity of PPS, the biogenic amine and angiotensinergic systems are activated. A decrease in PPS intensity normalizes deviations in all immunological parameters. The levels of n-Abs for the pain (β-endorphin) and analgesic (orphanin) systems are significant only at low PPS. Monitoring the individual profile of n-Abs to endogenous regulators allows us to obtain an objective picture of the pain status of the patient's body., (© 2024. Pleiades Publishing, Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
28. N-(3-((3-(trifluoromethyl)phenyl)selanyl)prop-2-yn-1-yl) benzamide induces antidepressant-like effect in mice: involvement of the serotonergic system.
- Author
-
Pires CS, da Rocha MJ, Presa MH, Zuge NP, Kuntz NEB, Godoi B, Bortolatto CF, and Brüning CA
- Subjects
- Animals, Male, Mice, Swimming, Organoselenium Compounds pharmacology, Serotonin metabolism, Depression drug therapy, Disease Models, Animal, Behavior, Animal drug effects, Serotonin Antagonists pharmacology, Hindlimb Suspension, Antidepressive Agents pharmacology, Benzamides pharmacology, Dose-Response Relationship, Drug
- Abstract
Rationale: Major Depressive Disorder (MDD) significantly impairs the quality of life for those affected. While the exact causes of MDD are not fully understood, the deficit of monoamines, especially serotonin and noradrenaline, is widely accepted. Resistance to long-term treatments and adverse effects are often observed, highlighting the need for new pharmacological therapies. Synthetic organic compounds containing selenium have exhibited pharmacological properties, including potential antidepressant effects., Objective: To evaluate the antidepressant-like effect of N-(3-((3-(trifluoromethyl)phenyl)selenyl)prop-2-yn-1-yl) benzamide (CF
3 SePB) in mice and the involvement of the serotonergic and noradrenergic systems., Methods: Male Swiss mice were treated with CF3 SePB (1-50 mg/kg, i.g.) and 30 min later the forced swimming test (FST) or tail suspension test (TST) was performed. To investigate the involvement of the serotonergic and noradrenergic systems in the antidepressant-like effect of CF3 SePB, mice were pre-treated with p-CPA (a 5-HT depletor, 100 mg/kg, i.p.) or the receptor antagonists WAY100635 (0.1 mg/kg, s.c., a 5-HT1A receptor antagonist), ketanserin (1 mg/kg, i.p., a 5-HT2A/2C receptor antagonist), ondansetron (1 mg/kg, i.p., a 5-HT3 receptor antagonist), GR110838 (0.1 mg/kg, i.p., a 5-HT4 receptor antagonist), prazosin (1 mg/kg, i.p., an α1 -adrenergic receptor antagonist), yohimbine (1 mg/kg, i.p., an α2 -adrenergic receptor antagonist) and propranolol (2 mg/kg, i.p., a non-selective beta-adrenergic receptor antagonist) at specific times before CF3 SePB (50 mg/kg, i.g.), and after 30 min of CF3 SePB administration the FST was performed., Results: CF3 SePB showed an antidepressant-like effect in both FST and TST and this effect was related to the modulation of the serotonergic system, specially the 5-HT1A and 5-HT3 receptors. None of the noradrenergic antagonists prevented the antidepressant-like effect of CF3 SePB. The compound exhibited a low potential for inducing acute toxicity in adult female Swiss mice., Conclusion: This study pointed a new compound with antidepressant-like effect, and it could be considered for the development of new antidepressants., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2024
- Full Text
- View/download PDF
29. Microbiome composition and central serotonergic activity in patients with depression and type 1 diabetes.
- Author
-
Flasbeck V, Hirsch J, Petrak F, Meier JJ, Herpertz S, Gatermann S, and Juckel G
- Subjects
- Humans, Male, Female, Adult, Middle Aged, Serotonin metabolism, Depressive Disorder, Major microbiology, Depressive Disorder, Major physiopathology, Depressive Disorder, Major metabolism, Feces microbiology, Brain-Gut Axis physiology, Young Adult, Diabetes Mellitus, Type 1 metabolism, Diabetes Mellitus, Type 1 microbiology, Diabetes Mellitus, Type 1 physiopathology, Gastrointestinal Microbiome physiology, Evoked Potentials, Auditory physiology
- Abstract
The role of gut-brain axis functioning gains growing attention in research on the pathophysiology of major depressive disorders. Here, especially consequences of altered microbiota composition on tryptophan metabolism resulting in altered serotonergic neurotransmission in the central nervous system (CNS) have reached a central position. Previous research, however, mainly focused on either microbiota and peripheral serotonin levels or central serotonergic neurotransmission. The present study aimed to combine the analysis of microbiota composition and central serotonergic activity using a valid neurophysiological indicator. We recruited 19 adult patients with type 1 diabetes and depression (D + D; 7 males), 19 patients with type 1 diabetes (D-; 7 male), and 20 healthy participants (HC; 7 males). Next to the analysis of fecal microbiota regarding α- and β-diversity, the loudness dependence of auditory evoked potential (LDAEP) was investigated, a non-invasive measurement of central serotonergic activity. High α-diversity was associated with high LDAEP, i.e., low serotonergic activity, in patients with diabetes and additional depression. Furthermore, relative abundances of bacterial families belonging to Bacteroidetes, Proteobacteria and Firmicutes were shown to have an impact on central serotonergic activity. This finding was supported by a tendency indicating an association of central serotonergic activity with the Bacteroidetes-Firmicutes ratio in both patients' groups. Together, this data suggests that the guts' microbiota composition might play an important role in regulating the central serotonergic activity in the brain., (© 2023. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
30. Depression and type 2 diabetes: A causal relationship and mechanistic pathway.
- Author
-
Khawagi WY, Al-Kuraishy HM, Hussein NR, Al-Gareeb AI, Atef E, Elhussieny O, Alexiou A, Papadakis M, Jabir MS, Alshehri AA, Saad HM, and Batiha GE
- Subjects
- Humans, Stress, Psychological complications, Stress, Psychological physiopathology, Hypothalamo-Hypophyseal System metabolism, Hypothalamo-Hypophyseal System physiopathology, Brain metabolism, Oxidative Stress physiology, Risk Factors, Hyperglycemia metabolism, Pituitary-Adrenal System physiopathology, Pituitary-Adrenal System metabolism, Depressive Disorder etiology, Serotonin metabolism, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 metabolism, Depression etiology, Insulin Resistance
- Abstract
Depression is a mood disorder that may increase risk for the development of insulin resistance (IR) and type 2 diabetes (T2D), and vice versa. However, the mechanistic pathway linking depression and T2D is not fully elucidated. The aim of this narrative review, therefore, was to discuss the possible link between depression and T2D. The coexistence of T2D and depression is twice as great compared to the occurrence of either condition independently. Hyperglycaemia and dyslipidaemia promote the incidence of depression by enhancing inflammation and reducing brain serotonin (5-hydroxytryptamine [5HT]). Dysregulation of insulin signalling in T2D impairs brain 5HT signalling, leading to the development of depression. Furthermore, depression is associated with the development of hyperglycaemia and poor glycaemic control. Psychological stress and depression promote the development of T2D. In conclusion, T2D could be a potential risk factor for the development of depression through the induction of inflammatory reactions and oxidative stress that affect brain neurotransmission. In addition, chronic stress in depression may induce the development of T2D through dysregulation of the hypothalamic-pituitary-adrenal axis and increase circulating cortisol levels, which triggers IR and T2D., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
31. Low-frequency (5-Hz) stimulation of ventrolateral periaqueductal gray modulates the descending serotonergic system in the peripheral neuropathic pain.
- Author
-
Park M, Koh CS, Chang H, Kim TJ, Mun W, Chang JW, and Jung HH
- Subjects
- Animals, Male, Rats, Deep Brain Stimulation methods, Disease Models, Animal, Hyperalgesia physiopathology, Hyperalgesia metabolism, Serotonin metabolism, Spinal Cord metabolism, Periaqueductal Gray metabolism, Periaqueductal Gray drug effects, Rats, Sprague-Dawley, Neuralgia therapy, Neuralgia metabolism, Neuralgia physiopathology
- Abstract
Abstract: Neuropathic pain is a type of chronic pain that entails severe prolonged sensory dysfunctions caused by a lesion of the somatosensory system. Many of those suffering from the condition do not experience significant improvement with existing medications, resulting in various side effects. In this study, Sprague-Dawley male rats were used, and long-term deep brain stimulation of the ventrolateral periaqueductal gray was conducted in a rat model of spared nerve injury. We found that 5-Hz deep brain stimulation effectively modulated mechanical allodynia and induced neuronal activation in the rostral ventromedial medulla, restoring impaired descending serotonergic system. At the spinal level, glial cells were still activated but only the 5-HT1a receptor in the spinal cord was activated, implying its inhibitory role in mechanical allodynia. This study found that peripheral neuropathy caused dysfunction in the descending serotonergic system, and prolonged stimulation of ventrolateral periaqueductal gray can modulate the pathway in an efficient manner. This work would provide new opportunities for the development of targeted and effective treatments for this debilitating disease, possibly giving us lower chances of side effects from repeated high-frequency stimulation or long-term use of medication., (Copyright © 2024 International Association for the Study of Pain.)
- Published
- 2024
- Full Text
- View/download PDF
32. The serotonergic neurons derived from rhombomere 2 are localized in the median raphe and project to the dorsal pallium in zebrafish.
- Author
-
Shibayama K, Nakajo H, Tanimoto Y, Kakinuma H, Shiraki T, Tsuboi T, and Okamoto H
- Subjects
- Animals, Neural Pathways physiology, Zebrafish Proteins genetics, Zebrafish Proteins metabolism, Serotonin metabolism, Habenula cytology, Habenula physiology, Zebrafish, Serotonergic Neurons physiology, Animals, Genetically Modified, Raphe Nuclei cytology
- Abstract
The serotonergic neurons in the raphe nucleus are implicated in various cognitive functions such as learning and emotion. In vertebrates, the raphe nucleus is divided into the dorsal raphe and the median raphe. In contrast to the abundance of knowledge on the functions of the dorsal raphe, the roles of the serotonergic neurons in the median raphe are relatively unknown. The studies using zebrafish revealed that the median raphe serotonergic neurons receive input from the two distinct pathways from the habenula and the IPN. The use of zebrafish may reveal the function of the Hb-IPN-median raphe pathway. To clarify the functions of the median raphe serotonergic neurons, it is necessary to distinguish them from those in the dorsal raphe. Most median raphe serotonergic neurons originate from rhombomere 2 in mice, and we generated the transgenic zebrafish which can label the serotonergic neurons derived from rhombomere 2. In this study, we found the serotonergic neurons derived from rhombomere 2 are localized in the median raphe and project axons to the rostral dorsal pallium in zebrafish. This study suggests that this transgenic system has the potential to specifically reveal the function and information processing of the Hb-IPN-raphe-telencephalon circuit in learning., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
33. Serotonin reuptake inhibitors improve muscle stem cell function and muscle regeneration in male mice.
- Author
-
Fefeu M, Blatzer M, Kneppers A, Briand D, Rocheteau P, Haroche A, Hardy D, Juchet-Martin M, Danckaert A, Coudoré F, Tutakhail A, Huchet C, Lafoux A, Mounier R, Mir O, Gaillard R, and Chrétien F
- Subjects
- Animals, Male, Mice, Mice, Inbred C57BL, Stem Cells drug effects, Stem Cells metabolism, Stem Cells cytology, Neovascularization, Physiologic drug effects, Selective Serotonin Reuptake Inhibitors pharmacology, Regeneration drug effects, Muscle, Skeletal drug effects, Muscle, Skeletal metabolism, Fluoxetine pharmacology, Serotonin metabolism
- Abstract
Serotonin reuptake inhibitor antidepressants such as fluoxetine are widely used to treat mood disorders. The mechanisms of action include an increase in extracellular level of serotonin, neurogenesis, and growth of vessels in the brain. We investigated whether fluoxetine could have broader peripheral regenerative properties. Following prolonged administration of fluoxetine in male mice, we showed that fluoxetine increases the number of muscle stem cells and muscle angiogenesis, associated with positive changes in skeletal muscle function. Fluoxetine also improved skeletal muscle regeneration after single and multiples injuries with an increased muscle stem cells pool and vessel density associated with reduced fibrotic lesions and inflammation. Mice devoid of peripheral serotonin treated with fluoxetine did not exhibit beneficial effects during muscle regeneration. Specifically, pharmacological, and genetic inactivation of the 5-HT1B subtype serotonin receptor also abolished the enhanced regenerative process induced by fluoxetine. We highlight here a regenerative property of serotonin on skeletal muscle., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
34. Copper Overload Increased Rat Striatal Levels of Both Dopamine and Its Main Metabolite Homovanillic Acid in Extracellular Fluid.
- Author
-
Cruces-Sande A, Garrido-Gil P, Sierra-Paredes G, Vázquez-Agra N, Hermida-Ameijeiras Á, Pose-Reino A, Méndez-Álvarez E, and Soto-Otero R
- Subjects
- Animals, Rats, Male, 3,4-Dihydroxyphenylacetic Acid metabolism, Rats, Wistar, Serotonin metabolism, Norepinephrine metabolism, Dopamine metabolism, Copper metabolism, Homovanillic Acid metabolism, Extracellular Fluid metabolism, Corpus Striatum metabolism
- Abstract
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 CuCl
2 /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.- Published
- 2024
- Full Text
- View/download PDF
35. Serotonergic amplification of odor-evoked neural responses maps onto flexible behavioral outcomes.
- Author
-
Bessonova Y and Raman B
- Subjects
- Animals, Behavior, Animal physiology, Smell physiology, Serotonin metabolism, Odorants analysis, Grasshoppers physiology
- Abstract
Behavioral responses to many odorants are not fixed but are flexible, varying based on organismal needs. How such variations arise and the role of various neuromodulators in achieving flexible neural-to-behavioral mapping is not fully understood. In this study, we examined how serotonin modulates the neural and behavioral responses to odorants in locusts ( Schistocerca americana ). Our results indicated that serotonin can increase or decrease appetitive behavior in an odor-specific manner. On the other hand, in the antennal lobe, serotonergic modulation enhanced odor-evoked response strength but left the temporal features or the combinatorial response profiles unperturbed. This result suggests that serotonin allows for sensitive and robust recognition of odorants. Nevertheless, the uniform neural response amplification appeared to be at odds with the observed stimulus-specific behavioral modulation. We show that a simple linear model with neural ensembles segregated based on behavioral relevance is sufficient to explain the serotonin-mediated flexible mapping between neural and behavioral responses., Competing Interests: YB, BR No competing interests declared, (© 2023, Bessonova and Raman.)
- Published
- 2024
- Full Text
- View/download PDF
36. Harnessing intestinal tryptophan catabolism to relieve atherosclerosis in mice.
- Author
-
Chajadine M, Laurans L, Radecke T, Mouttoulingam N, Al-Rifai R, Bacquer E, Delaroque C, Rytter H, Bredon M, Knosp C, Vilar J, Fontaine C, Suffee N, Vandestienne M, Esposito B, Dairou J, Launay JM, Callebert J, Tedgui A, Ait-Oufella H, Sokol H, Chassaing B, and Taleb S
- Subjects
- Animals, Mice, Kynurenine metabolism, Male, Gastrointestinal Microbiome, Indoles pharmacology, Inflammation metabolism, Mice, Knockout, Intestines pathology, T-Lymphocytes metabolism, T-Lymphocytes immunology, Disease Models, Animal, Tryptophan metabolism, Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism, Indoleamine-Pyrrole 2,3,-Dioxygenase genetics, Atherosclerosis metabolism, Atherosclerosis pathology, Atherosclerosis genetics, Atherosclerosis drug therapy, Diet, High-Fat adverse effects, Serotonin metabolism, Intestinal Mucosa metabolism, Mice, Inbred C57BL
- Abstract
Tryptophan (Trp) is an essential amino acid, whose metabolism is a key gatekeeper of intestinal homeostasis. Yet, its systemic effects, particularly on atherosclerosis, remain unknown. Here we show that high-fat diet (HFD) increases the activity of intestinal indoleamine 2, 3-dioxygenase 1 (IDO), which shifts Trp metabolism from the production of microbiota-derived indole metabolites towards kynurenine production. Under HFD, the specific deletion of IDO in intestinal epithelial cells leads to intestinal inflammation, impaired intestinal barrier, augmented lesional T lymphocytes and atherosclerosis. This is associated with an increase in serotonin production and a decrease in indole metabolites, thus hijacking Trp for the serotonin pathway. Inhibition of intestinal serotonin production or supplementation with indole derivatives alleviates plaque inflammation and atherosclerosis. In summary, we uncover a pivotal role of intestinal IDO in the fine-tuning of Trp metabolism with systemic effects on atherosclerosis, paving the way for new therapeutic strategies to relieve gut-associated inflammatory diseases., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
37. Curcumin Reduces Depression in Obese Patients with Type 2 Diabetes: A Randomized Controlled Trial.
- Author
-
Yaikwawong M, Jansarikit L, Jirawatnotai S, and Chuengsamarn S
- Subjects
- Humans, Male, Double-Blind Method, Female, Middle Aged, Malondialdehyde blood, Oxidative Stress drug effects, Serotonin metabolism, Serotonin blood, Antidepressive Agents therapeutic use, Antidepressive Agents pharmacology, Adult, Glutathione Peroxidase blood, Glutathione Peroxidase metabolism, Superoxide Dismutase blood, Superoxide Dismutase metabolism, Cytokines blood, Curcumin pharmacology, Curcumin therapeutic use, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Obesity complications, Obesity drug therapy, Depression drug therapy, Depression etiology, Antioxidants, Biomarkers blood
- Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
38. Differential Impact of Serotonin Signaling Methylphenidate on Young versus Adult: Insights from Behavioral and Dorsal Raphe Nucleus Neuronal Recordings from Freely Behaving Rats.
- Author
-
Dafny N, Elizondo GM, and Perez-Vasquez C
- Subjects
- Animals, Rats, Male, Neurons drug effects, Neurons metabolism, Serotonergic Neurons drug effects, Serotonergic Neurons metabolism, Rats, Sprague-Dawley, Signal Transduction drug effects, Age Factors, Methylphenidate pharmacology, Dorsal Raphe Nucleus drug effects, Dorsal Raphe Nucleus metabolism, Serotonin metabolism, Behavior, Animal drug effects
- Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
39. Dorsal raphe nucleus-hippocampus serotonergic circuit underlies the depressive and cognitive impairments in 5×FAD male mice.
- Author
-
Chen M, Wang C, Lin Y, Chen Y, Xie W, Huang X, Zhang F, Fu C, Zhuang K, Zou T, Can D, Li H, Wu S, Luo C, and Zhang J
- Subjects
- Animals, Male, Mice, Hippocampus metabolism, Serotonin metabolism, Optogenetics, Neural Pathways metabolism, Neural Pathways physiopathology, Dorsal Raphe Nucleus metabolism, Cognitive Dysfunction genetics, Cognitive Dysfunction metabolism, Cognitive Dysfunction psychology, Cognitive Dysfunction physiopathology, Serotonergic Neurons metabolism, Serotonergic Neurons physiology, Depression metabolism, Depression genetics, Depression psychology, Mice, Transgenic, Disease Models, Animal, Alzheimer Disease genetics, Alzheimer Disease metabolism, Alzheimer Disease psychology
- Abstract
Background: Depressive symptoms often occur in patients with Alzheimer's disease (AD) and exacerbate the pathogenesis of AD. However, the neural circuit mechanisms underlying the AD-associated depression remain unclear. The serotonergic system plays crucial roles in both AD and depression., Methods: We used a combination of in vivo trans-synaptic circuit-dissecting anatomical approaches, chemogenetic manipulations, optogenetic manipulations, pharmacological methods, behavioral testing, and electrophysiological recording to investigate dorsal raphe nucleus serotonergic circuit in AD-associated depression in AD mouse model., Results: We found that the activity of dorsal raphe nucleus serotonin neurons (DRN
5-HT ) and their projections to the dorsal hippocampal CA1 (dCA1) terminals (DRN5-HT -dCA1CaMKII ) both decreased in brains of early 5×FAD mice. Chemogenetic or optogenetic activation of the DRN5-HT -dCA1CaMKII neural circuit attenuated the depressive symptoms and cognitive impairments in 5×FAD mice through serotonin receptor 1B (5-HT1B R) and 4 (5-HT4 R). Pharmacological activation of 5-HT1B R or 5-HT4 R attenuated the depressive symptoms and cognitive impairments in 5×FAD mice by regulating the DRN5-HT -dCA1CaMKII neural circuit to improve synaptic plasticity., Conclusions: These findings provide a new mechanistic connection between depression and AD and provide potential pharmaceutical prevention targets for AD., (© 2024. The Author(s).)- Published
- 2024
- Full Text
- View/download PDF
40. Regulation of stress-induced sleep perturbations by dorsal raphe VGLUT3 neurons in male mice.
- Author
-
Henderson F, Dumas S, Gangarossa G, Bernard V, Pujol M, Poirel O, Pietrancosta N, El Mestikawy S, Daumas S, and Fabre V
- Subjects
- Animals, Male, Mice, Serotonin metabolism, Mice, Inbred C57BL, Amino Acid Transport Systems, Acidic metabolism, Amino Acid Transport Systems, Acidic genetics, Dorsal Raphe Nucleus metabolism, Stress, Psychological metabolism, Neurons metabolism, Sleep physiology
- Abstract
Exposure to stressors has profound effects on sleep that have been linked to serotonin (5-HT) neurons of the dorsal raphe nucleus (DR). However, the DR also comprises glutamatergic neurons expressing vesicular glutamate transporter type 3 (DR
VGLUT3 ), leading us to examine their role. Cell-type-specific tracing revealed that DRVGLUT3 neurons project to brain areas regulating arousal and stress. We found that chemogenetic activation of DRVGLUT3 neurons mimics stress-induced sleep perturbations. Furthermore, deleting VGLUT3 in the DR attenuated stress-induced sleep perturbations, especially after social defeat stress. In the DR, VGLUT3 is found in subsets of 5-HT and non-5-HT neurons. We observed that both populations are activated by acute stress, including those projecting to the ventral tegmental area. However, deleting VGLUT3 in 5-HT neurons minimally affected sleep regulation. These findings suggest that VGLUT3 expression in the DR drives stress-induced sleep perturbations, possibly involving non-5-HT DRVGLUT3 neurons., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
41. The Influence of BMP6 on Serotonin and Glucose Metabolism.
- Author
-
Milešević M, Matić Jelić I, Rumenović V, Ivanjko N, Vukičević S, and Bordukalo-Nikšić T
- Subjects
- Animals, Mice, Rats, Mice, Knockout, Cell Line, Tumor, Male, Insulin Secretion drug effects, Serotonin metabolism, Glucose metabolism, Bone Morphogenetic Protein 6 metabolism, Bone Morphogenetic Protein 6 genetics, Insulin-Secreting Cells metabolism, Insulin-Secreting Cells drug effects, Insulin metabolism
- Abstract
Previous studies have suggested a potential role of bone morphogenetic protein 6 (BMP6) in glucose metabolism, which also seems to be regulated by serotonin (5-hydroxytryptamine, 5HT), a biogenic amine with multiple roles in the organism. In this study, we explored possible interactions between BMP6, serotonin, and glucose metabolism regulation. The effect of BMP6 or 5HT on pancreatic β-cells has been studied in vitro using the INS-1 832/13 rat insulinoma cell line. Studies in vivo have been performed on mice with the global deletion of the Bmp6 gene (BMP6-/-) and included glucose and insulin tolerance tests, gene expression studies using RT-PCR, immunohistochemistry, and ELISA analyses. We have shown that BMP6 and 5HT treatments have the opposite effect on insulin secretion from INS-1 cells. The effect of BMP6 on the 5HT system in vivo depends on the tissue studied, with no observable systemic effect on peripheral 5HT metabolism. BMP6 deficiency does not cause diabetic changes, although a mild difference in insulin tolerance test between BMP6-/- and WT mice was observed. In conclusion, BMP6 does not directly influence glucose metabolism, but there is a possibility that its deletion causes slowly developing changes in glucose and serotonin metabolism, which would become more expressed with ageing.
- Published
- 2024
- Full Text
- View/download PDF
42. The GLP-1 Receptor Agonist Liraglutide Decreases Primary Bile Acids and Serotonin in the Colon Independently of Feeding in Mice.
- Author
-
Nonogaki K and Kaji T
- Subjects
- Animals, Mice, Male, Organic Anion Transporters, Sodium-Dependent metabolism, Fibroblast Growth Factors metabolism, Receptors, Cytoplasmic and Nuclear metabolism, Receptors, Cytoplasmic and Nuclear agonists, Tryptophan metabolism, Tryptophan pharmacology, Tryptophan analogs & derivatives, Mice, Inbred C57BL, Ileum metabolism, Ileum drug effects, Liver metabolism, Liver drug effects, Cholic Acids, Membrane Transport Proteins, Symporters, Liraglutide pharmacology, Serotonin metabolism, Bile Acids and Salts metabolism, Colon metabolism, Colon drug effects, Glucagon-Like Peptide-1 Receptor metabolism, Glucagon-Like Peptide-1 Receptor agonists
- Abstract
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 β-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/β, 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.
- Published
- 2024
- Full Text
- View/download PDF
43. Biosensors for psychiatric biomarkers in mental health monitoring.
- Author
-
Wang L, Hu Y, Jiang N, and Yetisen AK
- Subjects
- Humans, Dopamine analysis, Electrochemical Techniques methods, Mental Health, Serotonin analysis, Serotonin blood, Serotonin metabolism, Biomarkers analysis, Biosensing Techniques instrumentation, Biosensing Techniques methods, Mental Disorders diagnosis, Mental Disorders physiopathology
- Abstract
Psychiatric disorders are associated with serve disturbances in cognition, emotional control, and/or behavior regulation, yet few routine clinical tools are available for the real-time evaluation and early-stage diagnosis of mental health. Abnormal levels of relevant biomarkers may imply biological, neurological, and developmental dysfunctions of psychiatric patients. Exploring biosensors that can provide rapid, in-situ, and real-time monitoring of psychiatric biomarkers is therefore vital for prevention, diagnosis, treatment, and prognosis of mental disorders. Recently, psychiatric biosensors with high sensitivity, selectivity, and reproducibility have been widely developed, which are mainly based on electrochemical and optical sensing technologies. This review presented psychiatric disorders with high morbidity, disability, and mortality, followed by describing pathophysiology in a biomarker-implying manner. The latest biosensors developed for the detection of representative psychiatric biomarkers (e.g., cortisol, dopamine, and serotonin) were comprehensively summarized and compared in their sensitivities, sensing technologies, applicable biological platforms, and integrative readouts. These well-developed biosensors are promising for facilitating the clinical utility and commercialization of point-of-care diagnostics. It is anticipated that mental healthcare could be gradually improved in multiple perspectives, ranging from innovations in psychiatric biosensors in terms of biometric elements, transducing principles, and flexible readouts, to the construction of 'Big-Data' networks utilized for sharing intractable psychiatric indicators and cases., Competing Interests: Declaration of competing interest The authors declare no competing financial interests regarding the work described in this manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
44. Bioinformatics and LC-QTOF-MS based discovery of pharmacodynamic and Q-markers of Pitongshu against functional dyspepsia.
- Author
-
Chen SH, Wu HS, Jiang XF, Zhou C, Bian XR, He X, Li B, Dong YJ, Wang KG, Shen SH, Lv GY, and Zhi YH
- Subjects
- Animals, Mice, Male, Computational Biology, Molecular Docking Simulation, Chromatography, Liquid methods, Biomarkers blood, Serotonin blood, Serotonin metabolism, Disease Models, Animal, Mass Spectrometry methods, Dyspepsia drug therapy, Drugs, Chinese Herbal pharmacology
- Abstract
Ethnopharmacological Relevance: Pitongshu (PTS) is a clinically effective empirical formula for the treatment of FD. The efficacy and safety of PTS have been demonstrated in randomized, controlled, double-blind trials, but there is a lack of understanding of the systematic evaluation of the efficacy of PTS and its material basis., Objective: To investigate the efficacy of PTS in Functional dyspepsia (FD) mice and possible Q-markers., Method: In this study, we used "irregular feeding + chronic unpredictable chronic stimulation" to establish a mice model of FD with hepatogastric disharmony. The efficacy of PTS was assessed from hair condition, behavioral, pain, gastrointestinal function, and serum 5-HT, GAS, MTL levels in mice by instillation of different doses of PTS. In addition, the composition of drugs in blood was analyzed by LC-QTOF-MS and potential Q-markers were selected by combining network pharmacology, molecular docking and actual content., Result: Our study showed that different doses of PTS increased pain threshold and writhing latency, decreased the number of writhings, increased gastric emptying rate and small intestinal propulsion rate, decreased total acidity of gastric contents and gastric acid secretion, and increased serum levels of 5-HT, GAS, and MTL in mice to different degrees. Enrichment analysis showed that PTS may be anti-FD through multiple pathways such as Serotonergic synapse, thyroid hormone signaling pathway, cholinergic synapse, and dopaminergic synapse. In addition, potential active ingredient substances were explored by LC-QTOF-MS combined with bioinformatics. Combined with the actual contentselected six constituents, hesperidin, neohesperidin, naringin, paeoniflorin, magnolol and honokiol, possible as Q-markers., Conclusion: PTS may exert its anti-FD effects through multi-component, multi-target and multi-pathway". Constituents, hesperidin, neohesperidin, naringin, paeoniflorin, magnolol and honokiol may be the Q-markers of its anti-FD effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
45. ERβ activation improves nonylphenol-induced depression and neurotransmitter secretion disruption via the TPH2/5-HT pathway.
- Author
-
Yu J, Zhang Y, Yao H, Zhang Z, Yang X, Zhu W, and Xu J
- Subjects
- Animals, Male, Rats, Neurotransmitter Agents metabolism, Signal Transduction drug effects, Cell Line, Tumor, Nitriles toxicity, Nitriles pharmacology, Propionates toxicity, Propionates pharmacology, Pyrazoles, Pyrimidines, Tryptophan Hydroxylase metabolism, Estrogen Receptor beta metabolism, Phenols toxicity, Rats, Sprague-Dawley, Serotonin metabolism, Depression chemically induced, Depression drug therapy, Depression metabolism
- Abstract
The aim of this study is to investigate the role of estrogen receptor β (ERβ) in nonylphenol (NP) - induced depression - like behavior in rats and its impact on the regulation of the TPH2/5-HT pathway. In the in vitro experiment, rat basophilic leukaemia cells (RBL-2H3) cells were divided into the four groups: blank group, NP group (20 μM), ERβ agonist group (0.01 μM), and NP+ERβ agonist group (20 μM+0.01 μM). For the in vivo experiment, 72 adult male Sprague-Dawley rats were randomly divided into following six groups: the Control, NP (40 mg/kg) group, ERβ agonist (2 mg/kg, Diarylpropionitrile (DPN)) group, ERβ inhibitor (0.1 mg/kg, 4-(2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-3-yl) phenol (PHTPP)) group, NP+ERβ agonist (40 mg/kg NP + 2 mg/kg DPN) group, and NP+ERβ inhibitor (40 mg/kg NP + 0.1 mg/kg PHTPP) group, with 12 rats in each group. Each rat in drug group were given NP by gavage and/or received a single intraperitoneal injection of DPN 2 mg/kg or PHTPP 0.1 mg/kg. Both in vivo and in vitro, NP group showed a decrease in the expression levels of ERβ, tryptophan hydroxylase (TPH1), and tryptophan hydroxylase-2 (TPH2) genes and proteins, and reduced levels of DA, NE, and 5-hydroxytryptophan (5-HT) neurotransmitters. RBL-2H3 cells showed signs of cell shrinkage, with rounded cells, increased suspension and more loosely arranged cells. The effectiveness of the ERβ agonist stimulation exhibited an increase exceeding 60% in RBL-2H3 cells. The application of ERβ agonist resulted in an alleviation the aforementioned alterations. ERβ agonist activated the TPH2/5-HT signaling pathways. Compared to the control group, the NP content in the brain tissue of the NP group was significantly increased. The latency to eat for the rats was longer and the amount of food consumed was lower, and the rats had prolonged immobility time in the behavioral experiment of rats. The expression levels of ERβ, TPH1, TPH2, 5-HT and 5-HITT proteins were decreased in the NP group, suggesting NP-induced depression-like behaviours as well as disturbances in the secretion of serum hormones and monoamine neurotransmitters. In the NP group, the midline raphe nucleus showed an elongated nucleus with a dark purplish-blue colour, nuclear atrophy, displacement and pale cytoplasm. ERβ might ameliorate NP-induced depression-like behaviors, and secretion disorders of serum hormones and monoamine neurotransmitters via activating TPH2/5-HT signaling pathways., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)
- Published
- 2024
- Full Text
- View/download PDF
46. Lesions of the lateral habenula excite dopamine neurons in the ventral tegmental area and serotonin neurons in the dorsal raphe nuclei in hemiparkinsonian rats.
- Author
-
Tan H, Du C, Zhang L, Guo Y, Yang Y, Sun Q, Zhang Q, and Li L
- Subjects
- Animals, Male, Rats, Oxidopamine toxicity, Parkinsonian Disorders physiopathology, Parkinsonian Disorders metabolism, Parkinsonian Disorders chemically induced, Parkinsonian Disorders pathology, Prefrontal Cortex metabolism, Neural Pathways metabolism, Neural Pathways physiopathology, Ventral Tegmental Area metabolism, Habenula metabolism, Dopaminergic Neurons metabolism, Dopaminergic Neurons pathology, Dorsal Raphe Nucleus metabolism, Serotonergic Neurons metabolism, Serotonergic Neurons physiology, Serotonin metabolism, Dopamine metabolism, Rats, Sprague-Dawley
- Abstract
The lateral habenula (LHb) projects to the ventral tegmental area (VTA) and dorsal raphe nuclei (DRN) that deliver dopamine (DA) and serotonin (5-HT) to cortical and limbic regions such as the medial prefrontal cortex (mPFC), hippocampus and basolateral amygdala (BLA). Dysfunctions of VTA-related mesocorticolimbic dopaminergic and DRN-related serotonergic systems contribute to non-motor symptoms in Parkinson's disease (PD). However, how the LHb affects the VTA and DRN in PD remains unclear. Here, we used electrophysiological and neurochemical approaches to explore the effects of LHb lesions on the firing activity of VTA and DRN neurons, as well as the levels of DA and 5-HT in related brain regions in unilateral 6-hydroxydopamie (6-OHDA)-induced PD rats. We found that compared to sham lesions, lesions of the LHb increased the firing rate of DA neurons in the VTA and 5-HT neurons in the DRN, but decreased the firing rate of GABAergic neurons in the same nucleus. In addition, lesions of the LHb increased the levels of DA and 5-HT in the mPFC, ventral hippocampus and BLA compared to sham lesions. These findings suggest that lesions of the LHb enhance the activity of mesocorticolimbic dopaminergic and serotonergic systems in PD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
47. Lactobacillus plantarum AR495 improves colonic transport hyperactivity in irritable bowel syndrome through tryptophan metabolism.
- Author
-
Zhang H, Xia Y, Wang G, Xiong Z, Wei G, Liao Z, Qian Y, Cai Z, and Ai L
- Subjects
- Animals, Rats, Humans, Male, Female, Adult, Middle Aged, Disease Models, Animal, Feces microbiology, Young Adult, Irritable Bowel Syndrome metabolism, Irritable Bowel Syndrome therapy, Irritable Bowel Syndrome microbiology, Lactobacillus plantarum metabolism, Tryptophan metabolism, Probiotics pharmacology, Colon metabolism, Colon microbiology, Serotonin metabolism, Rats, Sprague-Dawley
- Abstract
Lactobacillus plantarum AR495 is a widely used probiotic for the treatment of various digestive diseases, including irritable bowel syndrome (IBS). However, the specific mechanisms of L. plantarum AR495 in alleviating IBS remain unclear. Abnormal intestinal tryptophan metabolism can cause disordered immune responses, gastrointestinal peristalsis, digestion and sensation, which is closely related to IBS pathogenesis. The aim of this study is to explore the effects and mechanisms of L. plantarum AR495 in regulating tryptophan metabolism. Primarily, tryptophan and its related metabolites in patients with IBS and healthy people were analyzed, and an IBS rat model of acetic acid enema plus restraint stress was established to explore the alleviation pathway of L. plantarum AR495 in tryptophan metabolism. It was found that the 5-HT pathway was significantly changed, and the 5-HTP and 5-HT metabolites were significantly increased in the feces of patients with IBS, which were consistent with the results obtained for the IBS rat model. Maladjusted 5-HT could increase intestinal peristalsis and lead to an increase in the fecal water content and shapeless stool in rats. On the contrary, these two metabolites could be restored to normal levels via intragastric administration of L. plantarum AR495. Further study of the metabolic pathway showed that L. plantarum AR495 could effectively reduce the abundance of 5-HT by inhibiting the expression of enterochromaffin cells rather than promoting its decomposition. In addition, the results showed that L. plantarum AR495 did not affect the expression of SERT. To sum up, L. plantarum AR495 could restore the normal levels of 5-HT by inhibiting the abnormal proliferation of enterochromaffin cells and the excessive activation of TPH1 to inhibit the intestinal peristalsis in IBS. These findings provide insights for the use of probiotics in the treatment of IBS and other diarrheal diseases.
- Published
- 2024
- Full Text
- View/download PDF
48. The Role of Gut Microbiome in Sleep Quality and Health: Dietary Strategies for Microbiota Support.
- Author
-
Sejbuk M, Siebieszuk A, and Witkowska AM
- Subjects
- Humans, Dietary Fiber administration & dosage, Melatonin, Feeding Behavior physiology, Polyphenols, Sleep physiology, Fatty Acids, Volatile metabolism, Serotonin metabolism, Gastrointestinal Microbiome physiology, Sleep Quality, Diet
- Abstract
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.
- Published
- 2024
- Full Text
- View/download PDF
49. New insights into the involvement of serotonin and BDNF-TrkB signalling in cannabidiol's antidepressant effect.
- Author
-
Guldager MB, Biojone C, da Silva NR, Godoy LD, and Joca S
- Subjects
- Animals, Humans, Cannabidiol pharmacology, Antidepressive Agents pharmacology, Brain-Derived Neurotrophic Factor metabolism, Serotonin metabolism, Signal Transduction drug effects, Receptor, trkB metabolism
- Abstract
Cannabidiol (CBD) is a phytocannabinoid devoid of psychostimulant properties and is currently under investigation as a potential antidepressant drug. However, the mechanisms underlying CBD's antidepressant effects are not yet well understood. CBD targets include a variety of receptors, enzymes, and transporters, with different binding-affinities. Neurochemical and pharmacological evidence indicates that both serotonin and BDNF-TrkB signalling in the prefrontal cortex are necessary for the antidepressant effects induced by CBD in animal models. Herein, we reviewed the current literature to dissect if these are independent mechanisms or if CBD-induced modulation of the serotonergic neurotransmission could mediate its neuroplastic effects through subsequent regulation of BDNF-TrkB signalling, thus culminating in rapid neuroplastic changes. It is hypothesized that: a) CBD interaction with serotonin receptors on neurons of the dorsal raphe nuclei and the resulting disinhibition of serotonergic neurons would promote rapid serotonin release in the PFC and hence its neuroplastic and antidepressant effects; b) CBD facilitates BDNF-TRKB signalling, especially in the PFC, which rapidly triggers neurochemical and neuroplastic effects. These hypotheses are discussed with perspectives for new drug development and clinical applications., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)
- Published
- 2024
- Full Text
- View/download PDF
50. Involvement of serotonergic receptors in depressive processes and their modulation by β-arrestins: A review.
- Author
-
Tejeda-Martínez AR, Ramos-Molina AR, Brand-Rubalcava PA, and Flores-Soto ME
- Subjects
- Humans, Serotonin metabolism, Signal Transduction physiology, Depressive Disorder metabolism, Depressive Disorder physiopathology, Brain metabolism, Depression metabolism, beta-Arrestins metabolism, Receptors, Serotonin metabolism
- Abstract
Over time, several studies have been conducted to demonstrate the functions of the neurotransmitter 5-hydroxytryptamine (5-HT), better known as serotonin. This neurotransmitter is associated with the modulation of various social and physiological behaviors, and its dysregulation has consequences at the behavioral level, leading to various neurophysiological disorders. Disorders such as anxiety, depression, schizophrenia, epilepsy, sexual disorders, and eating disorders, have been closely linked to variations in 5-HT concentrations and modifications in brain structures, including the raphe nuclei (RN), prefrontal cortex, basal ganglia, hippocampus, and hypothalamus, among others. The involvement of β-arrestin proteins has been implicated in the modulation of the serotonergic receptor response, as well as the activation of different signaling pathways related to the serotonergic system, this is particularly relevant in depressive disorders. This review will cover the implications of alterations in 5-HT receptor expression in depressive disorders in one hand and how β-arrestin proteins modulate the response mediated by these receptors in the other hand., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2024
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.