Serotonin Activity Research Articles

Linking the reversal of gestational insulin resistance to postpartum depression.

Postpartum depression (PPD) constitutes a significant mental health disorder affecting almost one fifth of pregnancies globally. Despite extensive research, the precise etiological mechanisms underlying PPD remain elusive. However, several risk factors like genetic predisposition, hormonal fluctuations, and stress-related environmental and psychosocial triggers have been found to be implicated in its development. MAIN: Recently, an increased risk of PPD has been reported to be associated with gestational diabetes mellitus (GDM), which is characterized by the disruption of glucose metabolism, primarily attributed to the emergence of insulin resistance (IR). While IR during pregnancy seems to be an evolutionary adaptative mechanism to handle the profound metabolic alterations during pregnancy, its subsequent resolution following delivery necessitates a reconfiguration of the metabolic landscape in both peripheral tissues and the central nervous system (CNS). Considering the pivotal roles of energy metabolism, particularly glucose metabolism, in CNS functions, we propose a novel model that such pronounced changes in IR and the associated glucose metabolism seen postpartum might account for PPD development. This concept is based on the profound influences from insulin and glucose metabolism on brain functions, potentially via modulating neurotransmitter actions of dopamine and serotonin. Their sudden postpartum disruption is likely to be linked to mood changes, as observed in PPD. The detailed pathogenesis of PPD might be multifactorial and still remains to be fully elucidated. Nevertheless, our hypothesis might account in part for an additional etiological factor to PPD development. If our concept is validated, it can provide guidance for future PPD prevention, diagnosis, and intervention.

PET Imaging of the Serotonin 1A Receptor in Major Depressive Disorder: Hierarchical Multivariate Analysis of [11C]WAY100635 Overcomes Outcome Measure Discrepancies

Abstract The serotonin 1A receptor has been linked to both the pathophysiology of major depressive disorder (MDD) and the antidepressant action of serotonin reuptake inhibitors. Most PET studies of the serotonin 1A receptor in MDD used the receptor antagonist radioligand, [carbonyl-11C]WAY100635; however the interpretation of the combined results has been contentious owing to reports of higher or lower binding in MDD with different outcome measures. The reasons for these divergent results originate from several sources, including properties of the radiotracer itself, which complicate its quantification and interpretation; as well as from previously reported differences between MDD and healthy volunteers in both reference tissue binding and plasma free fraction, which are typically assumed not to differ. Recently, we have developed two novel hierarchical multivariate methods which we validated for the quantification and analysis of [11C]WAY100635, which show better accuracy and inferential efficiency compared to standard analysis approaches. Importantly, these new methods should theoretically be more resilient to many of the factors thought to have caused the discrepancies observed in previous studies. We sought to apply these methods in the largest [11C]WAY100635 sample to date, consisting of 160 individuals, including 103 MDD patients, of whom 50 were not-recently-medicated and 53 were antidepressant-exposed, as well as 57 healthy volunteers. While the outcome measure discrepancies were substantial using conventional univariate analysis, our multivariate analysis techniques instead yielded highly consistent results across PET outcome measures and across pharmacokinetic models, with all approaches showing higher serotonin 1A autoreceptor binding potential in the raphe nuclei of not-recently-medicated MDD patients relative to both healthy volunteers and antidepressant-exposed MDD patients. Moreover, with the additional precision of estimates afforded by this approach, we can show that while binding is also higher in projection areas in this group, these group differences are approximately half of those in the raphe nuclei, which are statistically distinguishable from one another. These results are consistent with the biological role of the serotonin 1A autoreceptor in the raphe nuclei in regulating serotonin neuron firing and release, and with preclinical and clinical evidence of deficient serotonin activity in MDD due to over expression of autoreceptors resulting from genetic and/or epigenetic effects. These results are also consistent with downregulation of autoreceptors as a mechanism of action of selective serotonin reuptake inhibitors. In summary, the results using multivariate analysis approaches therefore demonstrate both face and convergent validity, and may serve to provide a resolution and consensus interpretation for the disparate results of previous studies examining the serotonin 1A receptor in MDD.

Serotonin syndrome caused by escitalopram in Parkinson’s disease psychosis: a case report

BackgroundSerotonin syndrome and Parkinson’s disease (PD) are two diseases whose symptoms partially overlap; this poses challenges in distinguishing them in clinical practice. Early manifestations such as tremor, akathisia, diaphoresis, hypertonia and hyperreflexia are common in mild-to-moderate serotonin syndrome and can also occur in PD. Without prompt recognition and treatment, serotonin syndrome can rapidly progress, potentially leading to severe complications such as multiple organ failure within hours. Given their disparate treatment strategies, accurate clinical distinction is crucial for effective treatment. This case study explores a patient with serotonin syndrome triggered by escitalopram in the context of PD psychosis (PDP), providing insights into diagnosis and treatment planning.Case presentationA 75-year-old Asian woman with a one-year history of PD, a two-month history of PDP, and a six-year history of depression presented with symptoms including hyperreflexia, tremor, hypertonia, impaired level of consciousness, and inappropriate behavior following a recent one-month adjustment in medication. Initially suspected of being drug-induced parkinsonism or worsening PD, therapeutic drug monitoring revealed warning levels of escitalopram. Subsequent diagnoses confirmed serotonin syndrome. This syndrome may result from increased cortical serotonin activity at the serotonin2A receptor due to dopamine and serotonin imbalances in PDP, compounded by increased dopamine-mediated serotonin release. Additionally, being an intermediate metabolizer of cytochrome P450 enzyme 2C19, the patient experienced excessive escitalopram accumulation, exacerbating her condition.ConclusionsThis case underscores the critical need to differentiate between symptoms of serotonin syndrome and PD, particularly in manifestations like tremor and hypertonia. Careful consideration of receptor profiles in patients with PDP is essential when selecting antidepressants to mitigate the risk of serotonin syndrome.

Striatal Serotonin Release Signals Reward Value.

Serotonin modulates diverse phenotypes and functions including depressive, aggressive, impulsive, and feeding behaviors, all of which have reward-related components. To date, research has focused on understanding these effects by measuring and manipulating dorsal raphe serotonin neurons and using single-receptor approaches. These studies have led to a better understanding of the heterogeneity of serotonin actions on behavior; however, they leave open many questions about the timing and location of serotonin's actions modulating the neural circuits that drive these behaviors. Recent advances in genetically encoded fluorescent biosensors, including the GPCR activation-based sensor for serotonin (GRAB-5-HT), enable the measurement of serotonin release in mice on a timescale compatible with a single rewarding event without corelease confounds. Given substantial evidence from slice electrophysiology experiments showing that serotonin influences neural activity of the striatal circuitry, and the known role of the dorsal medial striatal (DMS) in reward-directed behavior, we focused on understanding the parameters and timing that govern serotonin release in the DMS in the context of reward consumption, external reward value, internal state, and cued reward. Overall, we found that serotonin release is associated with each of these and encodes reward anticipation, value, approach, and consumption in the DMS.

DNA Sequence Variations Affecting Serotonin Transporter Transcriptional Regulation and Activity: Do They Impact Alcohol Addiction?

Genetic features of alcohol dependence have been extensively investigated in recent years. A large body of studies has underlined the important role of genetic variants not only in metabolic pathways but also in the neurobiology of alcohol dependence, mediated by the neuronal circuits regulating reward and craving. Serotonin transporter (5-HTT), encoded by the SLC6A4 gene (Solute carrier family 6-neurotransmitter transporter-member 4), is targeted by antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs) and plays a pivotal role in serotoninergic transmission; it has been associated with psychiatric diseases and alcohol dependence. Transcriptional regulation and expression of 5-HTT depend not only on epigenetic modifications, among which DNA methylation (CpG and non-CpG) is primarily involved, but also on sequence variations occurring in intron/exon regions and in untranslated regions in 5' and 3', being the first sequences important for the splicing machinery and the last for the binding of transcription factors and micro RNAs. This work intends to shed light on the role of sequence variations known to affect the expression or function of 5-HTT in alcohol-dependent individuals. We found a statistically significant difference in the allelic (p = 0.0083) and genotypic (p = 0.0151) frequencies of the tri-allelic polymorphism, with higher function alleles and genotypes more represented in the control population. Furthermore, we identified three haplotypes more frequent in subjects with AUD (p < 0.0001) and one more frequent in the control population (p < 0.0001). The results obtained for the tri-allelic polymorphism in alcohol dependence confirm what is already present in part of the literature. The role of haplotypes requires further studies to be clarified.

The multifaceted effects of fluoxetine treatment on cognitive functions.

Fluoxetine, the prototypical selective serotonin reuptake inhibitor (SSRI), is widely used to treat major depressive disorder (MDD) and a variety of other central nervous system conditions, primarily due to its established clinical safety profile. Although its efficacy in treating depression is well-recognized, the impact of fluoxetine on cognitive functions remains inconsistent and elusive. In this review, we first examine the well-substantiated biological mechanisms underlying fluoxetine's antidepressant effects, which include serotonin reuptake inhibition and activation of TrkB receptors-key to brain-derived neurotrophic factor (BDNF) signaling. Subsequently, we delve into the cognitive side effects observed in both preclinical and clinical studies, affecting domains such as memory, attention, and executive functions. While certain studies indicate cognitive improvements in patients with underlying disorders, there is also evidence of negative effects, influenced by variables like gender, duration of treatment, age, disease pathology, and the specifics of cognitive testing. Significantly, the negative cognitive outcomes reported in preclinical research often involve healthy, non-diseased animals. This review underscores the necessity for heightened caution in fluoxetine prescription and further investigation into its potentially detrimental cognitive effects, even when used prophylactically.

Serotonin Influences Insulin Secretion in Rat Insulinoma INS-1E Cells.

Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine that plays a critical role in insulin secretion, energy metabolism, and mitochondrial biogenesis. However, the action of serotonin in insulin production and secretion by pancreatic β cells has not yet been elucidated. Here, we investigated how exogenous nanomolar serotonin concentrations regulate insulin synthesis and secretion in rat insulinoma INS-1E cells. Nanomolar serotonin concentrations (10 and 50 nM) significantly increased insulin protein expression above the constant levels in untreated control cells and decreased insulin protein levels in the media. The reductions in insulin protein levels in the media may be associated with ubiquitin-mediated protein degradation. The levels of membrane vesicle trafficking-related proteins including Rab5, Rab3A, syntaxin6, clathrin, and EEA1 proteins were significantly decreased by serotonin treatment compared to the untreated control cells, whereas the expressions of Rab27A, GOPC, and p-caveolin-1 proteins were significantly reduced by serotonin treatment. In this condition, serotonin receptors, Gαq-coupled 5-HT2b receptor (Htr2b), and ligand-gated ion channel receptor Htr3a were significantly decreased by serotonin treatment. To confirm the serotonylation of Rab3A and Rab27A during insulin secretion, we investigated the protein levels of Rab3A and Rab27A, in which transglutaminase 2 (TGase2) serotonylated Rab3A but not Rab27A. The increases in ERK phosphorylation levels were consistent with increases in the expression of p-Akt. Also, the expression level of the Bcl-2 protein was significantly increased by 50 and 100 nM serotonin treatment compared to the untreated control cells, whereas the levels of Cu/Zn-SOD and Mn-SOD proteins decreased. These results indicate that nanomolar serotonin treatment regulates the insulin protein level but decreases this level in media through membrane vesicle trafficking-related proteins (Rab5, Rab3A, syntaxin6, clathrin, and EEA1), the Akt/ERK pathway, and Htr2b/Htr3a in INS-1E cells.

Teucrium polium Extract Ameliorates Neurobehavioral, Neurochemical Induced by Nicotine in Brain of Mice

Background: Smoking tobacco is a serious global health problem that is associated with psychiatric disorders and increased mortality rates. Nicotine, the main compound consumed during smoking, causes damage to different organs, especially the brain. The current study assessed the modulatory impact of Teucrium polium extract (TPE) on nicotine-induced behavioral and biochemical, alterations in mice brains. Methods: Twenty-four mice were divided into four groups and treated for three weeks. Group one was control, group two was subcutaneously injected with 2.5 mg/kg nicotine, group three received 100 mg/kg TPE orally, and group four was given 2.5 mg/kg of nicotine subcutaneously after an hour of oral administration of 100 mg/kg TPE. Result: The HPLC results of the plant extract showed the presence of 11 bioactive compounds. Nicotine administration increased anxiety and decreased locomotor activity and forelimb grip strength. Dopamine, serotonin, and acetylcholinesterase activity showed a significant decline in the nicotine-induced group. Treatment with TPE showed anxiolytic effects, modulated muscle strength and locomotor activity. Also, there was an increase in neurotransmitters compared with the nicotine group. In conclusion, TPE protected against nicotine-induced neurotoxicity through modulating behavior and neurotransmitter levels in mice.

Maternal treatment with a selective delta-opioid receptor agonist during gestation has a sex-specific pro-cognitive action in offspring: mechanisms involved.

Background: There is growing evidence that the treatment of several mental disorders can potentially benefit from activation of delta-opioid receptors. In the future, delta-agonists with a safe pharmacological profile can be used for the treatment of mood disorders in pregnant women. However, the data on prenatal exposure to delta-opioid agonists are missing. The present study is aimed to test the hypothesis that the activation of delta-opioid receptors during gravidity has positive effects on the behaviour accompanied by changes in glutamate and monoamine neurotransmission. Methods: Gestating Wistar rats were chronically treated with a selective delta-agonist SNC80 or vehicle. Adult male and female offspring underwent novel object recognition (for the assessment of cognition) and open field (for the assessment of anxiety and habituation) tests, followed by in vivo electrophysiological examination of the activity of hippocampal glutamate and midbrain serotonin (5-HT) and dopamine neurons. Results: We found that the maternal treatment with SNC80 did not affect the offspring's anxiety, habituation, and 5-HT neuronal firing activity. Female offspring of SNC80-treated dams exhibited improved novelty recognition associated with decreased firing rate and burst activity of glutamate and dopamine neurons. Conclusion: Maternal treatment with delta-opioid agonists during gestation may have a pro-cognitive effect on offspring without any negative effects on anxiety and habituation. The putative pro-cognitive effect might be mediated via mechanism(s) involving the firing activity of hippocampal glutamate and mesolimbic dopamine neurons.

Enhancing the action of serotonin by three different mechanisms prevents spontaneous seizure-induced mortality in Dravet mice.

Sudden unexpected death in epilepsy (SUDEP) is an underestimated complication of epilepsy. Previous studies have demonstrated that enhancement of serotonergic neurotransmission suppresses seizure-induced sudden death in evoked seizure models. However, it is unclear whether elevated serotonin (5-HT) function will prevent spontaneous seizure-induced mortality (SSIM), which is characteristic of human SUDEP. We examined the effects of 5-HT-enhancing agents that act by three different pharmacological mechanisms on SSIM in Dravet mice, which exhibit a high incidence of SUDEP, modeling human Dravet syndrome. Dravet mice of both sexes were evaluated for spontaneous seizure characterization and changes in SSIM incidence induced by agents that enhance 5-HT-mediated neurotransmission. Fluoxetine (a selective 5-HT reuptake inhibitor), fenfluramine (a 5-HT releaser and agonist), SR 57227 (a specific 5-HT3 receptor agonist), or saline (vehicle) was intraperitoneally administered over an 8-day period in Dravet mice, and the effect of these treatments on SSIM was examined. Spontaneous seizures in Dravet mice generally progressed from wild running to tonic seizures with or without SSIM. Fluoxetine at 30 mg/kg, but not at 20 or 5 mg/kg, significantly reduced SSIM compared with the vehicle control. Fenfluramine at 1-10 mg/kg, but not .2 mg/kg, fully protected Dravet mice from SSIM, with all mice surviving. Compared with the vehicle control, SR 57227 at 20 mg/kg, but not at 10 or 5 mg/kg, significantly lowered SSIM. The effect of these drugs on SSIM was independent of sex. Our data demonstrate that elevating serotonergic function by fluoxetine, fenfluramine, or SR 57227 significantly reduces or eliminates SSIM in Dravet mice in a sex-independent manner. These findings suggest that deficits in serotonergic neurotransmission likely play an important role in the pathogenesis of SSIM, and fluoxetine and fenfluramine, which are US Food and Drug Administration-approved medications, may potentially prevent SUDEP in at-risk patients.

Development of an Antioxidant-Rich Sugar-Free Plantain Candy and Assessment of Its Shelf Life in a Flexible Laminate.

Candy is a popular confection worldwide, and it would be beneficial to society if it were converted into a source of antioxidant molecules to eliminate its adverse health effects. The amount of antioxidants available even in fruit candies is questionable due to the high thermal processing losses they undergo and the presence of various food additives. Plantains (Musa paradisiaca) are less known as good sources of biotherapeutic antioxidants, namely l-tryptophan, serotonin and melatonin, and consumption of this highly nutritious fruit is limited to underdeveloped and developing countries. The objectives of this study are: to develop a functional antioxidant-rich sugar-free plantain-based candy with valuable contents of the mentioned biomolecules in synergy; and to ensure its extended shelf life without compromising its physicochemical properties and functionality by wrapping it with a suitable packaging laminate. To accomplish the first objective, lyophilized plantain powder, sorbitol and mannitol were used as base materials with minimal additives under minimal processing conditions to reduce processing loss. Sensory, proximate, physicochemical and phytochemical properties, including the antioxidant synergy among the mentioned biomolecules of the developed candies were evaluated. For the second objective, the candies were enclosed in two different flexible packaging laminates and the optimal packaging was determined based on the microbiological safety and sensory appeal of the wrapped candies. Subsequently, the above-mentioned properties of the packaged (in the most suitable laminate) candies were evaluated at regular time intervals during storage for assessment of their shelf life. The candy had a characteristic flavour of plantain, uniform dark brown colour, rich mouthfeel, pleasant aroma, moderately hard texture and moderate sweetness, along with high antioxidant activity and considerable content of l-tryptophan, serotonin and melatonin (present as a synergistic consortium). During storage of the packaged candy under ambient conditions, it remained microbiologically safe for up to 56 days, and also maintained sensory attributes, antioxidant activity and synergy compared to the control candy. This newly developed semi-hard sugar-free candy with high antioxidant content, containing three important antioxidants, namely l-tryptophan, serotonin and melatonin, could be a good source of biotherapeutic molecules and a substitute for commercial candies consumed globally.

Serotonin effects on human iPSC-derived neural cell functions: from mitochondria to depression.

Depression's link to serotonin dysregulation is well-known. The monoamine theory posits that depression results from impaired serotonin activity, leading to the development of antidepressants targeting serotonin levels. However, their limited efficacy suggests a more complex cause. Recent studies highlight mitochondria as key players in depression's pathophysiology. Mounting evidence indicates that mitochondrial dysfunction significantly correlates with major depressive disorder (MDD), underscoring its pivotal role in depression. Exploring the serotonin-mitochondrial connection, our study investigated the effects of chronic serotonin treatment on induced-pluripotent stem cell-derived astrocytes and neurons from healthy controls and two case study patients. One was a patient with antidepressant non-responding MDD ("Non-R") and another had a non-genetic mitochondrial disorder ("Mito"). The results revealed that serotonin altered the expression of genes related to mitochondrial function and dynamics in neurons and had an equalizing effect on calcium homeostasis in astrocytes, while ATP levels seemed increased. Serotonin significantly decreased cytosolic and mitochondrial calcium in neurons. Electrophysiological measurements evidenced that serotonin depolarized the resting membrane potential, increased both sodium and potassium current density and ultimately improved the overall excitability of neurons. Specifically, neurons from the Non-R patient appeared responsive to serotonin in vitro, which seemed to improve neurotransmission. While it is unclear how this translates to the systemic level and AD resistance mechanisms are not fully elucidated, our observations show that despite his treatment resistance, this patient's cortical neurons are responsive to serotonergic signals. In the Mito patient, evidence suggested that serotonin, by increasing excitability, exacerbated an existing hyperexcitability highlighting the importance of considering mitochondrial disorders in patients with MDD, and avoiding serotonin-increasing medication. Taken together, our findings suggested that serotonin positively affects calcium homeostasis in astrocytes and increases neuronal excitability. The latter effect must be considered carefully, as it could have beneficial or detrimental implications based on individual pathologies.

Membrane-Mediated Allosteric Action of Serotonin on a Noncognate G-Protein-Coupled Receptor.

The structure and dynamics of the lipid membrane can affect the activity of membrane proteins. Therefore, small lipophilic molecules that alter membrane properties (such as the neurotransmitter serotonin) can potentially modulate receptor activity without binding to the receptor. Here, we investigated how the activity of neuropeptide Y type 4 receptor (Y4R, reconstituted in lipid bicelles) is modulated by serotonin, which has no known interaction with Y4R. We found a serotonin-concentration-dependent decrease (down to 0.1 mM of serotonin) in the ligand affinity of Y4R. This effect correlates with a serotonin-induced reduction of the resistance of the bilayer to indentation (measured by atomic force microscopy) and bilayer thickness (measured by solid state NMR) in two different types of zwitterionic lipid bicelles. Our findings indicate a "membrane-mediated allosteric effect" of serotonin on the activation of Y4R and suggest the potential for developing pharmacophores, which can modulate cellular signaling without directly interacting with any receptor.

Global research in schizophrenia and serotonin: a bibliometric analysis.

Schizophrenia is a chronic mental illness that affects millions of individuals worldwide. The etiological origin of schizophrenia is heterogeneous, but it has been shown to be associated with dysfunction in serotonin activity, serotonin receptors, and serotonin metabolism in the brain. Bibliometric analysis is a tool used to scrutinise and analyse research activities and evidence in a specific research area. No existing bibliometric analyses have considered both serotonin and schizophrenia. We conducted a bibliometric analysis including 12,027 studies related to the schizophrenia-serotonin link published from the inception of the study to 2023 and available in the Scopus database. We used VOSviewer software to identify global trends, analyse the author and editors keywords, the most cited articles and author, as well as the most productive institutes and journals publishing research on schizophrenia-serotonin link. Most publications related to the link between schizophrenia and serotonin are focused on adult humans and examine topics such as antipsychotic agents, depression, and serotonin uptake inhibitors. The Journal of Clinical Psychiatry has published the most papers on the schizophrenia-serotonin relationship. Among nations, the United States is the leader in publications. King's College London is the institution with the highest number of publications, and H. Y. Meltzer is the most influential author. Growing trends in schizophrenia-serotonin research are personalised medicine, alternative medicine, transcranial magnetic stimulation, artificial intelligence, nervous system inflammation, brain-gut axis, and the gut microbiome. Since 1950, there have been several fluctuations in the number of published studies related to schizophrenia and serotonin. We believe that the development of novel medications and treatments for schizophrenia will be increased in the future, as well as research into genetic risks, psychological factors, and cranial neuroimaging components. Future schizophrenia and serotonin research is likely to focus on personalised medicine, alternative therapies, novel pathogenesis of schizophrenia, and the use of emerging technologies such as artificial intelligence.

The role of the GABAergic system on insomnia.

Sleep is an essential activity for the survival of mammals. Good sleep quality helps promote the performance of daily functions. In contrast, insufficient sleep reduces the efficiency of daily activities, causes various chronic diseases like Alzheimer's disease, and increases the risk of having accidents. The GABAergic system is the primary inhibitory neurotransmitter system in the central nervous system. It transits the gamma-aminobutyric acid (GABA) neurotransmitter via GABAA and GABAB receptors to counterbalance excitatory neurotransmitters, such as glutamate, noradrenaline, serotonin, acetylcholine, orexin, and dopamine, which release and increase arousal activities during sleep. Several studies emphasized that dysfunction of the GABAergic system is related to insomnia, the most prevalent sleep-related disorder. The GABAergic system comprises the GABA neurotransmitter, GABA receptors, GABA synthesis, and degradation. Many studies have demonstrated that GABA levels correlate with sleep quality, suggesting that modulating the GABAergic system may be a promising therapeutic approach for insomnia. In this article, we highlight the significance of sleep, the classification and pathology of insomnia, and the impact of the GABAergic system changes on sleep. In addition, we also review the medications that target the GABAergic systems for insomnia, including benzodiazepines (BZDs), non-BZDs, barbiturates, GABA supplements, and Chinese herbal medicines.

Role of Serotonergic System in Regulating Brain Tumor-Associated Neuroinflammatory Responses.

Serotonin signaling regulates wide arrays of both neural and extra-neural functions. Serotonin is also found to affect cancer progression directly as well as indirectly by modulating the immune cells. In the brain, serotonin plays a key role in regulating various functions; disturbance of the normal activities of serotonin leads to various mental illnesses, including the neuroinflammatory response in the central nervous system (CNS). The neuroinflammatory response can be initiated in various psychological illnesses and brain cancer. Serotonergic signaling can impact the functions of both glial as well as the immune cells. It can also affect the tumor immune microenvironment and the inflammatory response associated with brain cancers. Apart from this, many drugs used for treatment of psychological illness are known to modulate serotonergic system and can cross the blood-brain barrier. Understanding the role of serotonergic pathways in regulating neuroinflammatory response and brain cancer will provide a new paradigm in modulating the serotonergic components in treating brain cancer and associated inflammation-induced brain damages.

One-drop chemosensing of dapoxetine hydrochloride using opto-analysis by multi-channel μPAD decorated silver nanoparticles: introducing a paper-based microfluidic portable device/sensor toward naked-eye pharmaceutical analysis by lab-on-paper technology.

Dapoxetine (DPX) belongs to the selective serotonin reuptake inhibitor (SSRI) class and functions by blocking the serotonin transporter and increasing serotonin activity, thereby delaying ejaculation. Therefore, monitoring of the concentration of DPX in human biofluids is important for clinicians. In this study, application of silver nanoparticles with the morphology of prisms (AgNPrs) for the sensitive measurement of DPX using colorimetric chemosensing and the spectrophotometric method was investigated. Also, DPX was determined in real samples using the spectrophotometry method. Based on the obtained results, all of the detection process in colorimetric assay is related to morphological reform of AgNPrs after it's specific electrostatic and covalent interaction with DPX as analyte. The UV-vis results indicate that the proposed AgNPrs-based chemosensing system has a wide range of linearity (0.01 μM to 1 mM) with a low limit of quantification of 0.01 μM in human urine samples, which is suitable for clinical analysis of this drug in human urine samples. It is important to point out that, this chemosensing strategy showed inappropriate analytical results for the detection of DPX in human urine samples which is a novelty of this platform. Finally, the optimized microfluidic paper-based analytical device (μPAD) was integrated with the colorimetric analysis of DPX to provide a time/color system for estimating analyte concentration by a portable substrate toward in situ and on-site biomedical analysis. Interestingly, the analytical validation tests showed appropriate results with great stability, which may facilitate commercialization of the engineered substrate. For the first time, in order to provide a simple and portable colorimetric/spectrophotometric recognition system to sensitive determination of DPX, an optimized pump-less microfluidic paper-based colorimetric device (μPCD) was introduced and validated for the real-time biomedical analysis of this analyte. According to the obtained results, this alternative approach is suitable for therapeutic drug monitoring (TDM) and biomedical analysis by miniaturized and cost-beneficial devices.

Intermittent Restraint Stress and Recovery on GPCR Expression in Brain/Gut Axis of Mice: Activation of Adrenergic, Dopamine, Serotonin and Melatonin Receptors During Stress and Ease Response

Intermittent Restraint Stress and Recovery on GPCR Expression in Brain/Gut Axis of Mice: Activation of Adrenergic, Dopamine, Serotonin and Melatonin Receptors During Stress and Ease Response

Epigallocatechin-gallate attenuates rapamycin exacerbated high fat diet-induced autophagy, hormonal dysregulation, testicular and brain oxidative stress, and neurochemical changes in rats

This study investigated whether epigallocatechin-gallate (EGCG) could counteract the detrimental effects of high-fat diet (HFD)-induced obesity in rats exposed to rapamycin-induced reproductive and neuronal changes. Six rats per treatment group (n = 6) were utilized, in which groups 1 and 2 had dimethylsulfoxide (DMSO) (0.1%) and EGCG (80 mg/kg) respectively. Group 3 received HFD + 0.1% DMSO daily for 56 days. Group 4 received HFD + rapamycin (1 mg/kg) orally for 56 days. Rats in group 5 received HFD for 56 days and EGCG (80 mg/kg, p.o.) from days 29–56. Group 6 received the combination of HFD + rapamycin (56 days) with EGCG (80 mg/kg) from days 29–56. Cognitive loss was assessed using Y-maze-test (YMT). Afterwards, serum sex hormones, insulin-glucose balance, serotonin concentration, acetylcholinesterase activity, sperm features, antioxidants, and the markers of oxido-nitrergic, autophagy and apoptotic mediators were assessed. EGCG reversed rapamycin exacerbated HFD-induced alterations in spermatogenesis, insulin-glucose balance, reproductive hormones, oxido-nitrergic stress, and altered serotonin, acetylcholinesterase levels, and autophagic and apoptotic activities in rats' testes and brains respectively. EGCG significantly attenuated HFD-induced cognitive loss. The study showed that EGCG attenuated rapamycin-mediated HFD-induced spermatogenesis deficiency and cognitive impairment via normalization of reproductive hormones, testicular and brain oxidative stress, apoptotic, autophagic activities, with serotonin and cholinergic levels in rats.

Serotonin syndrome: A pharmacovigilance comparative study of drugs affecting serotonin levels.

Serotonin syndrome is a rare and potentially fatal adverse drug reaction caused by serotonergic drugs and is due to an increase in serotonin concentration or activation of the 5-HT receptor in the central nervous system. We analysed adverse events in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) data set to investigate the main drug classes related to reports of serotonin syndrome and the reporting risk in relation to age and sex. We analysed data from the FAERS database to evaluate the main drug classes related to reports of the serotonin syndrome, and the reporting risk in relation to age and sex. We found 8,997 cases of serotonin syndrome; selective serotonin reuptake inhibitors (SSRIs) was the class of drugs with most reports, followed by opioids and other antidepressants. The highest Reporting Odds Ratios (ROR) for drug classes was for monoamine oxidase (MAO) inhibitors (45.99, 95% confidence interval (CI): 41.21-51.33) and SSRIs (32.66, 95% CI: 31.33-34.04), while the ten active substances with the highest ROR were moclobemide, isocarboxazid, oxitriptane, tranylcypromine, melitracen, phenelzine, linezolid, amoxapine, reboxetine and tryptophan; with values of ROR ranging from 44.19 (95% CI: 25.38-76.94) of tryptophan to 388.36 (95% CI: 314.58-479.46) of moclobemide. The ROR for the most commonly involved drugs was higher in the group of older adults (65 > years old), and higher in males. Prescribers need to be vigilant about drugs that can raise serotonin concentration or influence serotonergic neurotransmission, also when using drugs with less well-known risk for serotonin syndrome, like linezolid and triptans.