Inhibition of Kv2.1 potassium channels by the antidepressant drug sertraline.

Sertraline is a commonly used antidepressant of the selective serotonin reuptake inhibitors (SSRIs) class. In this study, we have used the patch-clamp technique to assess the effects of sertraline on Kv2.1 channels heterologously expressed in HEK-293 cells and on the voltage-gated potassium currents (IKv) of Neuro 2a cells, which are predominantly mediated by Kv2.1 channels. Our results reveal that sertraline inhibits Kv2.1 channels in a concentration-dependent manner. The sertraline-induced inhibition was not voltage-dependent and did not require the channels to be open. The kinetics of activation and deactivation were accelerated and decelerated, respectively, by sertraline. Moreover, the inhibition by this drug was use-dependent. Notably, sertraline significantly modified the inactivation mechanism of Kv2.1 channels; the steady-state inactivation was shifted to hyperpolarized potentials, the closed-state inactivation was enhanced and accelerated, and the recovery from inactivation was slowed, suggesting that this is the main mechanism by which sertraline inhibits Kv2.1 channels. Overall, this study provides novel insights into the pharmacological actions of sertraline on Kv2.1 channels, shedding light on the intricate interaction between SSRIs and ion channel function.

Research Report: A Link between Sertraline Treatment and Susceptibility to (Mis)information.

Recent research revealed that several psycho-cognitive processes, such as insensitivity to positive and negative feedback, cognitive rigidity, pessimistic judgment bias, and anxiety, are involved in susceptibility to fake news. All of these processes have been previously associated with depressive disorder and are sensitive to serotoninergic manipulations. In the current study, a link between chronic treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline and susceptibility to true and fake news was examined. Herein, a sample of 1162 participants was recruited via Prolific Academic for an online study. Half of the sample reported taking sertraline (Zoloft) for at least 8 weeks (sertraline group), and the other half confirmed not taking any psychiatric medication (control group). The sertraline group was further divided according to their daily dosage (50, 100, 150, and 200 mg/day). All participants completed a susceptibility to misinformation scale, wherein they were asked to determine the veracity of the presented true and fake news and their willingness to behaviorally engage with the news. The results were compared between those of the sertraline groups and the control group. The results showed that sertraline groups did not differ significantly in the assessment of the truthfulness of information or their ability to discern the truth. However, those taking sertraline appeared to have a significantly increased likelihood of behavioral engagement with the information, and this effect was observed for both true and fake news. The research presented here represents the initial endeavor to comprehend the neurochemical foundation of the susceptibility to misinformation. The association between sertraline treatment and increased behavioral engagement with information observed in this study can be explained in light of previous studies showing positive correlations between serotonin (5-HT) system activity and the inclination to engage in social behaviors. It can also be attributed to the anxiolytic effects of sertraline treatment, which mitigate the fear of social judgment. The heightened behavioral engagement with information in people taking sertraline may, as part of a general phenomenon, also shape their interactions with fake news. Future longitudinal studies should reveal the specificity and exact causality of these interactions.

Sertraline Promotes Health and Longevity in Caenorhabditis elegans.

INTRODUCTION: While several antidepressants have been identified as potential geroprotectors, the effect and mechanism of sertraline on healthspan remain to be elucidated. Here, we explored the role of sertraline in the lifespan and healthspan of Caenorhabditis elegans. METHODS: The optimal effect concentration of sertraline was first screened in wild-type N2 worms under heat stress conditions. Then, we examined the effects of sertraline on lifespan, reproduction, lipofuscin accumulation, mobility, and stress resistance. Finally, the expression of serotonin signaling and aging-related genes was investigated to explore the underlying mechanism, and the lifespan assays were performed in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants. RESULTS: Sertraline extended the lifespan in C. elegans with concomitant extension of healthspan as indicated by increasing mobility and reducing fertility and lipofuscin accumulation, as well as enhanced resistance to different abiotic stresses. Mechanistically, ser-7 orchestrated sertraline-induced longevity via the regulation of insulin and AMPK pathways, and sertraline-induced lifespan extension in nematodes was abolished in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants. CONCLUSION: Sertraline promotes health and longevity in C. elegans through ser-7-insulin/AMPK pathways.

Temporal sequencing of change in trauma-related beliefs and therapeutic alliance during prolonged exposure and sertraline for chronic PTSD.

OBJECTIVE: Changes in trauma-related beliefs and therapeutic alliance have been found to temporally precede symptom reduction; however, it is likely these processes do not act in isolation but rather in interactive ways. METHODS: The present study examined the temporal relationships between negative posttraumatic cognitions (PTCI) and therapeutic alliance (WAI) in 142 patients who were part of a randomized trial comparing prolonged exposure (PE) to sertraline for chronic PTSD. RESULTS: Using time-lagged mixed regression models, improvements in the therapeutic alliance predicted subsequent improvements in trauma-related beliefs (d = 0.59), an effect accounted for by between-patient variability (d = 0.64) compared to within-patient variability (d = .04) giving weaker support to the causal role of alliance on outcome. Belief change did not predict improvements in alliance and neither model was moderated by treatment type. CONCLUSION: Findings suggest alliance may not be an independent driver of cognition change and point to the need for additional study of the impact of patient characteristics on treatment processes.

Investigation into the impact of proton pump inhibitors on sertraline transport across the blood-brain barrier.

As a widely used antidepressant that works by inhibiting the reuptake of serotonin, sertraline exerts an antidepressant effect depending on its concentration in the brain, which might be limited by the blood-brain barrier (BBB). It is highly possible to combine proton pump inhibitors (PPIs) with sertraline in clinical trials. Nevertheless, the role played by PPIs in regulating the transport of sertraline across the BBB remains unclear. Here, the impact of PPIs on the distribution of sertraline in the brain and the mechanisms involved were investigated. A mouse brain distribution study showed that Omeprazole (OME), Pantoprazole (PAN), Ilaprazole (ILA), and Esomeprazole (ESO) increased the area under the brain concentration-time curves (AUC) for sertraline by 2.02-, 3.18-, 3.04-, and 4.21-fold, respectively, after the 14-day administration of PPIs. Besides, PPIs significantly increased the permeability of sertraline in brain perfusion experiments, with PAN having the highest rank order, followed by ILA, OME, and ESO. In the tail suspension test (TST), co-administration PPI groups showed significantly shorter immobility time than the control group. In vitro, four PPIs inhibited sertraline efflux in breast cancer resistance protein (BCRP)-overexpressing MDCKII cells, and showed a mixed inhibition type. In this study, PPIs were further found to inhibit the mRNA and protein expression of brain BCRP. To sum up, the findings of this study revealed that PPIs could enhance the brain distribution and antidepressant effect of sertraline, which may be attributed to the inhibition of BCRP expression at the BBB by PPIs.

Brain metabolite levels in remitted psychotic depression with consideration of effects of antipsychotic medication.

BACKGROUND: The neurobiology of psychotic depression is not well understood and can be confounded by antipsychotics. Magnetic resonance spectroscopy (MRS) is an ideal tool to measure brain metabolites non-invasively. We cross-sectionally assessed brain metabolites in patients with remitted psychotic depression and controls. We also longitudinally assessed the effects of olanzapine versus placebo on brain metabolites. METHODS: Following remission, patients with psychotic depression were randomized to continue sertraline + olanzapine (n = 15) or switched to sertraline + placebo (n = 18), at which point they completed an MRS scan. Patients completed a second scan either 36 weeks later, relapse, or discontinuation. Where water-scaled metabolite levels were obtained and a Point-RESolved Spectroscopy sequence was utilized, choline, myo-inositol, glutamate + glutamine (Glx), N-acetylaspartate, and creatine were measured in the left dorsolateral prefrontal cortex (L-DLPFC) and dorsal anterior cingulate cortex (dACC). An ANCOVA was used to compare metabolites between patients (n = 40) and controls (n = 46). A linear mixed-model was used to compare olanzapine versus placebo groups. RESULTS: Cross-sectionally, patients (compared to controls) had higher myo-inositol (standardized mean difference [SMD] = 0.84; 95%CI = 0.25-1.44; p = 0.005) in the dACC but not different Glx, choline, N-acetylaspartate, and creatine. Longitudinally, patients randomized to placebo (compared to olanzapine) showed a significantly greater change with a reduction of creatine (SMD = 1.51; 95%CI = 0.71-2.31; p = 0.0002) in the dACC but not glutamate + glutamine, choline, myo-inositol, and N-acetylaspartate. CONCLUSIONS: Patients with remitted psychotic depression have higher myo-inositol than controls. Olanzapine may maintain creatine levels. Future studies are needed to further disentangle the mechanisms of action of olanzapine.

Intranasal administration of sertraline ensures sustained brain delivery and antidepressant effect in a mouse model of depression.

The pursuit of more potent and efficacious antidepressant therapies is of utmost significance. Herein, the intranasal (IN) route was investigated for sertraline brain delivery, encompassing a comparative pharmacokinetic study after a single-dose administration to mice by IN, intravenous (IV) (4.87 mg/kg) and oral (10 mg/kg) routes, and an efficacy/toxicity study to explore the therapeutic effect in mice subjected to the unpredictable chronic mild stress (UCMS) protocol. Neurotransmitters and melatonin were quantified in prefrontal cortex and plasma, respectively. A different drug biodistribution behavior was unveiled for a CNS-acting drug administered by means of the IN route. For the first time, IN administration of sertraline exhibited heightened systemic exposure (bioavailability = 166 %), and a sustained drug release into the brain, in opposition to IV and oral routes, avoiding drug fluctuation. The lower lung exposition (given by normalized area under the curve) observed after IN instillation envisions the reduction of sertraline pulmonary side effects and similarly other peripheral side effects. IN sertraline treatment displayed significant efficacy in ameliorating anhedonia after one week of administration while the 14-day IN treatment regimen translated into decreased immobility time and increased swimming time in the forced swimming test, suggesting an improvement of the depressive-like behavior displayed by the animal depressive-model. Remarkably, these effects were absent with oral sertraline, despite the higher used dose. Noteworthy neurotransmitter alterations were observed, with IN sertraline markedly reducing adrenaline in the prefrontal cortex, while serotonin and melatonin increased following both administration routes. With its sustained brain delivery and serotonin- and melatonin-enhancing potential, the innovative strategy of IN sertraline holds the potential not only to effectively address depressive symptoms but also to mitigate challenges inherent to classic treatments.

GABAergic neuroactive steroid response to sertraline in premenstrual dysphoric disorder.

RATIONALE: Premenstrual dysphoric disorder (PMDD) affects approximately 5% of menstruating individuals, with significant negative mood symptoms in the luteal phase of the menstrual cycle. PMDD's pathophysiology and treatment mechanisms are poorly characterized, but may involve altered neuroactive steroid function in the brain. Selective serotonin reuptake inhibitors (SSRIs), a first-line PMDD treatment, reportedly alter gamma-aminobutyric acid (GABA)ergic neuroactive steroid levels in PMDD. AIMS: The aims of this study were to determine whether the SSRI sertraline increased serum levels of neuroactive steroids that modulate the effect of GABA at GABA-A receptors (GABAAR) and if so, whether an increase was associated with improvement in PMDD symptoms. METHODS: Participants included controls and individuals with PMDD. Serum levels of 9 neuroactive steroids were measured (3α,5α-THP; 3α5ß-THP; pregnenolone; 3α,5α-androsterone; 3α,5ß-androsterone; 3α,5α-A-diol; 3α5ß-A-diol; 3α,5α-THDOC; 3α5ß-THDOC) in the follicular and luteal phases. In the subsequent luteal phase, neuroactive steroids were measured during sertraline treatment (50 mg sertraline from approximate ovulation to menses onset) in the PMDD group. Mixed models assessed associations among diagnostic group, menstrual cycle phase, and sertraline treatment. RESULTS: Participants included 38 controls and 32 women with PMDD. There were no significant differences in neuroactive steroid levels between controls and participants with PMDD in the luteal phase (p > 0.05). Within the PMDD group, sertraline treatment significantly increased serum pregnanolone levels and the pregnanolone:progesterone ratio, and decreased 3α,5α-androsterone. CONCLUSIONS: This was the first study to assess the impact of SSRI treatment on peripheral levels of GABAergic neuroactive steroids in PMDD. Within the PMDD group, sertraline treatment was associated with a significant increase in luteal phase serum pregnanolone levels and a significantly increased pregnanolone:progesterone ratio, a novel finding. Future research should examine alterations in the metabolic pathways among GABAergic neuroactive steroids in individuals with PMDD, in a placebo-controlled design.

Personalized Medicine in the Treatment of a Patient With Obsessive-Compulsive Disorder With Clomipramine.

Clomipramine (CIMI) is an effective treatment for obsessive-compulsive disorder in patients who have failed to respond to trials of selective serotonin transport inhibitors (eg, sertraline). The case presented here illustrates how knowledge of the pharmacodynamics and pharmacokinetics of CIMI in a specific patient can be used to personalize treatment to optimize the likelihood of efficacy (ie, maximum benefit to risk ratio). The approach described in this column considered: (1) the patient's diminished ability to clear CIMI and its major metabolite, desmethlyclomipramine due to a genetic deficiency in cytochrome P450 2D6 enzyme activity, and (2) the patient's ability to extensively convert CIMI to desmethlyclomipramine. That conversion impairs the ability to inhibit the serotonin transporter, the mechanism that is most likely responsible for the efficacy of CIMI in obsessive-compulsive disorder.

Sertraline Pre-Treatment Attenuates Hemorrhagic Transformation Induced in Rats after Cerebral Ischemia Reperfusion via Down Regulation of Neuronal CD163: Involvement of M1/M2 Polarization Interchange and Inhibiting Autophagy.

Cerebral ischemia reperfusion (I/R) is one of the neurovascular diseases which leads to severe brain deterioration. Haemorrhagic transformation (HT) is the main complication of ischemic stroke. It exacerbates by reperfusion, causing a more deleterious effect on the brain and death. The current study explored the protective effect of sertraline (Sert) against cerebral I/R in rats by inhibiting HT, together with the molecular pathways involved in this effect. Forty-eight wister male rats were divided into 4 groups: Sham, Sert + Sham, I/R, and Sert + I/R. The ischemic model was induced by bilateral occlusion of the common carotid artery for 20 min, then reperfusion for 24 h. Sertraline (20 mg/kg, p.o.) was administrated for 14 days before exposure to ischemia. Pre-treatment with Sert led to a significant attenuation of oxidative stress and inflammation. In addition, Sert attenuated phosphorylation of extracellular regulated kinases and nuclear factor kappa-p65 expression, consequently modulating microglial polarisation to M2 phenotype. Moreover, Sert prevented the hemorrhagic transformation of ischemic stroke as indicated by the notable decrease in neuronal expression of CD163, activity of Heme oxygenase-2 and matrix metalloproteinase-2 and 9 levels. In the same context, Sert decreased levels of autophagy and apoptotic markers. Furthermore, histological examination, Toluidine blue, and Prussian blue stain aligned with the results. In conclusion, Sert protected against cerebral I/R damage by attenuating oxidative stress, inflammation, autophagy, and apoptotic process. It is worth mentioning that our study was the first to show that Sert inhibited hemorrhagic transformation. The protective effect of sertraline against injury induced by cerebral ischemia reperfusion via inhibiting Hemorrhagic transformation.

Sertraline associated with gold nanoparticles reduce cellular toxicity and induce sex-specific responses in behavior and neuroinflammation biomarkers in a mouse model of anxiety.

This study aimed to evaluate the effects of sertraline associated with gold nanoparticles (AuNPs) in vitro cell viability and in vivo behavior and inflammatory biomarkers in a mouse model of anxiety. Sertraline associated with AuNPs were synthesized and characterized. For the in vitro study, NIH3T3 and HT-22 cells were treated with different doses of sertraline, AuNPs, and sertraline + AuNPs and their viability was evaluated using the MTT assay. For the in vivo study, pregnant Swiss mice were administered a single dose of lipopolysaccharide (LPS) on the ninth day of gestation. The female and male offspring were divided into five treatment groups on PND 60 and administered chronic treatment for 28 days. The animals were subjected to behavioral testing and were subsequently euthanized. Their brains were collected and analyzed for inflammatory biomarkers. Sertraline associated with AuNPs exhibited significant changes in surface characteristics and increased diameters. Different doses of sertraline + AuNPs showed higher cell viability in NIH3T3 and HT-22 cells compared with sertraline alone. The offspring of LPS-treated dams exhibited anxiety-like behavior and neuroinflammatory biomarker changes during adulthood, which were ameliorated via sertraline + AuNPs treatment. The treatment response was sex-dependent and brain region-specific. These results suggest that AuNPs, which demonstrate potential to bind to other molecules, low toxicity, and reduced inflammation, can be synergistically used with sertraline to improve drug efficacy and safety by decreasing neuroinflammation and sertraline toxicity.

Upregulation by duloxetine of the transforming growth factor-α-induced migration of hepatocellular carcinoma cells via enhancement of the c-Jun N-terminal kinase activity.

Duloxetine, a selective reuptake inhibitor for serotonin and norepinephrine, is a medication widely used for major depression. Currently, duloxetine is also recommended for pain related to chemotherapy-induced peripheral neuropathy or cancer. Previously, we showed that transforming growth factor-α (TGF-α) induces the migration of human hepatocellular carcinoma (HCC)-derived HuH7 cells through the activation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and AKT. In the present study, we investigate whether duloxetine affects cell migration and its mechanism. Duloxetine significantly enhanced the TGF-α-induced migration of HuH7 cells. Fluvoxamine and sertraline, specific inhibitors of serotonin reuptake, also upregulated the TGF-α-induced cell migration. On the contrary, reboxetine, a specific norepinephrine reuptake inhibitor, failed to affect cell migration. Duloxetine significantly amplified the TGF-α-stimulated phosphorylation of JNK, but not p38 MAPK and AKT. In addition, fluvoxamine and sertraline, but not reboxetine, enhanced the phosphorylation of JNK. SP600125, a JNK inhibitor, suppressed the enhancement by duloxetine, fluvoxamine, or sertraline of TGF-α-induced migration of HuH7 cells. Taken together, our results strongly suggest that duloxetine strengthens the TGF-α-induced activation of JNK via inhibition of serotonin reuptake in HCC cells, leading to the enhancement of cell migration.

Sertraline has fungicidal activity against Candida spp. and acts by inhibiting membrane and cell wall biosynthesis.

Aim: Our study evaluated the activity of sertraline (SER) alone and associated with antifungal drugs in planktonic Candida spp. strains, and investigated its mechanism of action. Materials & methods: Broth microdilution method and minimum fungicidal concentration/MIC ratio were used to assess SER anticandidal activity, and the interaction with antifungals was determined by fractional inhibitory concentration index. The mechanism of action was investigated by flow cytometry and in silico tests. Results: SER inhibited Candida spp. strains at low concentrations by the fungicidal effect and showed no loss of effectiveness when combined. Its action seemed to be related to the membrane and cell wall biosynthesis inhibition. Conclusion: SER has activity against Candida spp. isolated and associated with antifungals, and acts by causing cell wall and membrane damage.

The serotonin transporter sustains human brown adipose tissue thermogenesis.

Activation of brown adipose tissue (BAT) in humans is a strategy to treat obesity and metabolic disease. Here we show that the serotonin transporter (SERT), encoded by SLC6A4, prevents serotonin-mediated suppression of human BAT function. RNA sequencing of human primary brown and white adipocytes shows that SLC6A4 is highly expressed in human, but not murine, brown adipocytes and BAT. Serotonin decreases uncoupled respiration and reduces uncoupling protein 1 via the 5-HT2B receptor. SERT inhibition by the selective serotonin reuptake inhibitor (SSRI) sertraline prevents uptake of extracellular serotonin, thereby potentiating serotonin's suppressive effect on brown adipocytes. Furthermore, we see that sertraline reduces BAT activation in healthy volunteers, and SSRI-treated patients demonstrate no 18F-fluorodeoxyglucose uptake by BAT at room temperature, unlike matched controls. Inhibition of BAT thermogenesis may contribute to SSRI-induced weight gain and metabolic dysfunction, and reducing peripheral serotonin action may be an approach to treat obesity and metabolic disease.

Sertraline as a potential cancer therapeutic approach: Biological relevance of TCTP in breast cancer cell lines and tumors.

PURPOSE: This study aimed to evaluate the role of Translationally Controlled Tumor Protein (TCTP) in breast cancer (BC) and investigate the effects of sertraline, a serotonin selective reuptake inhibitor (SSRI), on BC cells. The objective was to assess the potential of sertraline as a therapeutic agent in BC treatment by examining its ability to inhibit TCTP expression and exert antitumor effects. MATERIAL AND METHODS: We utilized five different BC cell lines representing the molecular heterogeneity and distinct subtypes of BC, including luminal, normal-like, HER2-positive, and triple-negative BC. These subtypes play a crucial role in determining clinical treatment strategies and prognosis. RESULTS: The highest levels of TCTP were observed in triple-negative BC cell lines, known for their aggressive behavior. Sertraline treatment reduced TCTP expression in BC cell lines, significantly impacting cell viability, clonogenicity, and migration. Additionally, sertraline sensitized triple-negative BC cell lines to cytotoxic chemotherapeutic drugs (doxorubicin and cisplatin) suggesting its potential as an adjunctive therapy to enhance the chemotherapeutic response. Bioinformatic analysis of TCTP mRNA levels in TCGA BC data revealed a negative correlation between TCTP levels and patient survival, as well as between TCTP/tpt1 and Ki67. These findings contradict our data and previous studies indicating a correlation between TCTP protein levels and aggressiveness and poor prognosis in BC. CONCLUSIONS: Sertraline shows a promise as a potential therapeutic option for BC, particularly in triple-negative BC. Its ability to inhibit TCTP expression, enhance chemotherapeutic response, highlights its potential clinical utility in BC treatment, specifically in triple-negative BC subtype.

Chemical Imaging of Pharmaceuticals in Biofilms for Wastewater Treatment Using Secondary Ion Mass Spectrometry.

The occurrence of pharmaceuticals in the aquatic environment is a global water quality challenge for several reasons, such as deleterious effects on ecological and human health, antibiotic resistance development, and endocrine-disrupting effects on aquatic organisms. To optimize their removal from the water cycle, understanding the processes during biological wastewater treatment is crucial. Time-of-flight secondary ion mass spectrometry imaging was successfully applied to investigate and analyze the distribution of pharmaceuticals as well as endogenous molecules in the complex biological matrix of biofilms for wastewater treatment. Several compounds and their localization were identified in the biofilm section, including citalopram, ketoconazole, ketoconazole transformation products, and sertraline. The images revealed the pharmaceuticals gathered in distinct sites of the biofilm matrix. While citalopram penetrated the biofilm deeply, sertraline remained confined in its outer layer. Both pharmaceuticals seemed to mainly colocalize with phosphocholine lipids. Ketoconazole concentrated in small areas with high signal intensity. The approach outlined here presents a powerful strategy for visualizing the chemical composition of biofilms for wastewater treatment and demonstrates its promising utility for elucidating the mechanisms behind pharmaceutical and antimicrobial removal in biological wastewater treatment.

Development of sertraline analogues as potential anti-ischemic stroke agents.

Ischemic stroke (IS) is harmful to human health and social development, and there is no medicine available at present. To find the hit compound for treating ischemic stroke, we screened 28 FDA approved nervous system drugs by using an in vitro OGD-induced stroke model. Notably, our in vitro and in vivo studies demonstrated that low-dose sertraline had good neuroprotective activities, while high-dose sertraline showed significant toxicity. Interestingly, the same high-dose sertraline in the control group did not exhibit any obvious toxic effect. Therefore, it is important to modify the structure of sertraline to improve the activity and reduce the toxicity. Stereoisomers of sertraline were first investigated to analyze the influence of stereochemistry on the neuroprotective activities, which showed no obvious difference. Then we evaluated the activity of our previously reported sertraline analogues and found that introducing amide or alkane groups to the amino moiety might be beneficial to enhance the activity and reduce the toxicity. Thus, 10 new analogues were designed, synthesized, and evaluated. Among them, compound OY-201 showed the best safety and neuroprotective activity in both in vitro and in vivo models. Moreover, it exhibited good blood-brain barrier (BBB) permeability, indicating its potential for the development of anti-ischemic stroke drugs.

The effects of curcumin and sertraline on stress-induced changes in the stomach tissues of rats.

Exposure to stressors can cause functional disorders and structural damage to the stomach. Sertraline (SER) is an antidepressant and curcumin (CUR) is a natural compound with many properties. The current study aimed to investigate the impacts of stress, SER, and CUR on the stomach tissue using stereological methods. In total, 24 male and 24 female Sprague-Dawley rats were divided into four groups. In the control group, the rats were not exposed to stress. However, the animals in stress, SER and, CUR groups were exposed to daily stress and were orally fed with distilled water, SER (10 mg/kg/day), and CUR (100 mg/kg/day), respectively. The volume, surface area, and number of nerve, parietal, and chief cells were evaluated by stereological methods. Results showed that stress increased the stomach and its mucosa and submucosa volumes, while it decreased the surface area of the mucosa. Furthermore, this disorder increased the number of neurons in the submucosa and myenteric plexuses while it decreased the number of parietal and chief cells. However, treating stressed rats with SER or CUR could prevent these changes. The results showed that the consumption of SER or CUR could be used as a preventive or adjunctive treatment for stressful situations.

Antimicrobial Activity of Sertraline on Listeria monocytogenes.

We explored the antimicrobial activity of sertraline on Listeria monocytogenes and further investigated the effects of sertraline on biofilm formation and the virulence gene expression of L. monocytogenes. The minimum inhibitory concentration and minimum bactericidal concentration for sertraline against L. monocytogenes were in the range of 16-32 µg/mL and 64 µg/mL, respectively. Sertraline-dependent damage of the cell membrane and a decrease in intracellular ATP and pHin in L. monocytogenes were observed. In addition, sertraline reduced the biofilm formation efficiency of the L. monocytogenes strains. Importantly, low concentrations (0.1 µg/mL and 1 µg/mL) of sertraline significantly down-regulated the expression levels of various L. monocytogens virulence genes (prfA, actA, degU, flaA, sigB, ltrC and sufS). These results collectively suggest a role of sertraline for the control of L. monocytogenes in the food industry.

Individualized fMRI connectivity defines signatures of antidepressant and placebo responses in major depression.

Though sertraline is commonly prescribed in patients with major depressive disorder (MDD), its superiority over placebo is only marginal. This is in part due to the neurobiological heterogeneity of the individuals. Characterizing individual-unique functional architecture of the brain may help better dissect the heterogeneity, thereby defining treatment-predictive signatures to guide personalized medication. In this study, we investigate whether individualized brain functional connectivity (FC) can define more predictable signatures of antidepressant and placebo treatment in MDD. The data used in the present work were collected by the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study. Patients (N = 296) were randomly assigned to antidepressant sertraline or placebo double-blind treatment for 8 weeks. The whole-brain FC networks were constructed from pre-treatment resting-state functional magnetic resonance imaging (rs-fMRI). Then, FC was individualized by removing the common components extracted from the raw baseline FC to train regression-based connectivity predictive models. With individualized FC features, the established prediction models successfully identified signatures that explained 22% variance for the sertraline group and 31% variance for the placebo group in predicting HAMD17 change. Compared with the raw FC-based models, the individualized FC-defined signatures significantly improved the prediction performance, as confirmed by cross-validation. For sertraline treatment, predictive FC metrics were predominantly located in the left middle temporal cortex and right insula. For placebo, predictive FC metrics were primarily located in the bilateral cingulate cortex and left superior temporal cortex. Our findings demonstrated that through the removal of common FC components, individualization of FC metrics enhanced the prediction performance compared to raw FC. Associated with previous MDD clinical studies, our identified predictive biomarkers provided new insights into the neuropathology of antidepressant and placebo treatment.