antidepressant and proteomics

Chronic social isolation (CSIS)-induced alternation in synaptic and mitochondrial function of specific brain regions is associated with major depressive disorder (MDD). Despite the wide number of available medications, treating MDD remains an important challenge. Although fluoxetine (Flx) is the most frequently prescribed antidepressant, its mode of action is still unknown. To delineate affected molecular pathways of depressive-like behavior and identify potential targets upon Flx treatment, we performed a comparative proteomic analysis of hippocampal purified synaptic terminals (synaptosomes) of rats exposed to six weeks of CSIS, an animal model of depression, and/or followed by Flx treatment (lasting three weeks of six-week CSIS) to explore synaptic protein profile changes...

Major depressive disorder (MDD) is the psychiatric disorder with the highest prevalence in the world. Pharmacological antidepressant treatment (AD), such as selective serotonin reuptake inhibitors [SSRI, i.e., fluoxetine (Flx)] is the first line of treatment for MDD. Despite its efficacy, lack of AD response occurs in numerous patients characterizing Difficult-to-treat Depression. ElectroConvulsive Therapy (ECT) is a highly effective treatment inducing rapid improvement in depressive symptoms and high remission rates of ∼50-63% in patients with pharmaco-resistant depression...

Treatment of anxiety and depression predominantly centres around pharmacological interventions, which have faced criticism for their associated side effects, lack of efficacy and low tolerability. Saffron, which is reportedly well tolerated in humans, has been recognised for its antidepressant and anti-anxiety properties. Indeed, we previously reported upon the efficacy of saffron extract supplementation in healthy adults with subclinical anxiety. However, the molecular aetiology remains unclear. In a rodent model of low-grade chronic inflammation, we explored the impact of a saffron extract (Safr'Inside™) supplemented at a physiological dose, which equated to 22 ± 1...

Fluoxetine (Prozac™) is the only antidepressant approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD) in children. Despite its considerable efficacy as a selective serotonin reuptake inhibitor, the possible long-term effects of fluoxetine on brain development in children are poorly understood. In the current study, we aimed to delineate molecular mechanisms and protein biomarkers in the brains of juvenile rhesus macaques ( Macaca mulatta ) one year after the discontinuation of fluoxetine treatment using proteomic and phosphoproteomic profiling...

Antibiotic resistance is a global concern threatening public health. Horizontal gene transfer (HGT) between bacterial species contributes greatly to the dissemination of antibiotic resistance. Conjugation is one of the major HGT pathways responsible for the spread of antibiotic resistance genes (ARGs). Antidepressant drugs are commonly prescribed antipsychotics for major depressive disorders and are frequently detected in aquatic environments. However, little is known about how antidepressants stress bacteria and whether such effect can promote conjugation...

Human myeloperoxidase (MPO) utilizes hydrogen peroxide to oxidize organic compounds and as such plays an essential role in cell-component synthesis, in metabolic and elimination pathways, and in the front-line defence against pathogens. Moreover, MPO is increasingly being reported to play a role in inflammation. The enzymatic activity of MPO has also been shown to depend on its glycosylation. Mammalian MPO crystal structures deposited in the Protein Data Bank (PDB) present only a partial identification of their glycosylation...

Antidepressants have been reported to enhance stroke recovery independent of the presence of depressive symptoms. They have recently been proposed to exert their mood-stabilizing actions by inhibition of acid sphingomyelinase (ASM), which catalyzes the hydrolysis of sphingomyelin to ceramide. Their restorative action post-ischemia/reperfusion (I/R) still had to be defined. Mice subjected to middle cerebral artery occlusion or cerebral microvascular endothelial cells exposed to oxygen-glucose deprivation were treated with vehicle or with the chemically and pharmacologically distinct antidepressants amitriptyline, fluoxetine or desipramine...

Fluoxetine (Flx) is the most commonly used antidepressant to treat major depressive disorder. However, its molecular mechanisms of action are not defined as yet. A comparative proteomic approach was used to identify proteome changes in the prefrontal cortex (PFC) cytosolic and non-synaptic mitochondria (NSM)-enriched fractions of adult male Wistar rats following chronic social isolation (CSIS), a rat model of depression, and Flx treatment in CSIS and control rats, using liquid chromatography online tandem mass spectrometry...

Depression is a global public health issue with high morbidity and mortality, which tends to cause fatigue, inability to concentrate, insomnia, and loss of appetite, especially represented by major depressive disorder (MDD). Pathologically, depression is associated with hyperactivity of hypothalamic-pituitaryadrenal (HPA) axis, inflammation, loss of monoaminergic system, and disturbance of gut microbiota. Epidemiological studies have shown that regular tea drinking can reduce the risk of depression. Tea bioactive compounds (L-theanine, catechin, tea pigment and GABA) can regulate depression by inhibiting hyperactive HPA axis, reducing the inflammatory response, restoring the monoaminergic system, inhibiting monoamine oxidase levels, increasing the enrichment of intestinal flora and promoting microbial-gut-brain axis activity...

Major depressive disorder (MDD) is a complex and multifactorial psychiatric disorder that causes serious health, social, and economic concerns worldwide. The main treatment of the symptoms is through antidepressant (AD) drugs. However, not all patients respond properly to these drugs. Omic sciences are widely used to analyze not only biomarkers for the AD response but also their molecular mechanism. In this review, we aimed to focus on omics data to better understand the molecular mechanisms involving AD effects on MDD...

Emerging evidence suggests that dysfunction of the visual cortex may be involved in major depressive disorder (MDD). However, the underlying mechanisms remain unclear. We previously established that combined magnetic stimulation system treatment (c-MSST) resulted in an antidepressant effect in mice. In the present study, we found that V1-targeted c-MSST induced significant antidepressant effects in chronic unpredictable mild stress (CUMS)- and lipopolysaccharide (LPS)-treated mice. Proteomic screening investigation and repeatable validation revealed that expression of the V1 neuronal ATP-binding cassette transporter A1 (ABCA1) and apolipoprotein A-1 (ApoA1) was downregulated in CUMS mice, an effect that was normalized by c-MSST...

A major challenge in managing depression is that antidepressant drugs take a long time to exert their therapeutic effects. For the development of faster-acting treatments, it is crucial to get an improved understanding of the molecular mechanisms underlying antidepressant mode of action. Here, we used a novel mass spectrometry-based workflow to investigate how antidepressant treatment affects brain protein turnover at single-cell and subcellular resolution. We combined stable isotope metabolic labeling, quantitative Tandem Mass Spectrometry (qTMS) and Multi-isotope Imaging Mass Spectrometry (MIMS) to simultaneously quantify and image protein synthesis and turnover in hippocampi of mice treated with the antidepressant paroxetine...

Numerous emotional and cognitive processes mediated by the hippocampus present differences between sexes and can be markedly influenced by hormonal status in males and females of several species. In rodents, the dorsal hippocampus (dHPC) is known to contribute to the rapid antidepressant actions of the NMDA receptor antagonist ketamine. We and others have demonstrated a greater sensitivity to the fast-acting antidepressant ketamine in female versus male rats that is estrogen- and progesterone-dependent. However, the underlying mechanisms remain unclear...

Teleost fish skin-scales are essential for protection and homeostasis and the largest tissue in direct contact with the environment, but their potential as early indicators of pollutant exposure are hampered by limited knowledge about this model. This study evaluated multi-level impacts of in vivo exposure of European sea bass to fluoxetine (FLX, a selective serotonin-reuptake inhibitor and an emerging pollutant) and 17β-estradiol (E2, a natural hormone and representative of diverse estrogenic endocrine-disrupting pollutants)...

The proteomics data included in this article supplement the research article titled "Predictive protein markers for the severity of depression in mood disorders: A preliminary trans-diagnostic approach study (manuscript ID: JPSYCHIATRES-D-20-00437)." Plasma protein was analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This data article included 370 plasma protein profiles expressed in patients with bipolar II disorder (BD-II) and major depressive disorder (MDD). The tables present the comparison of protein expressions between BD-II and MDD, and the relationship between the severity of the depressive symptoms and protein expression...

Depression is a common psychopathological state or mood disorder syndrome. The serious risks to human life and the inadequacy of the existing antidepressant drugs have driven us to understand the pathogenesis of depression from a new perspective. Our research group has found disturbances in glucose catabolism in both depression and nephrotic syndrome. What are the specific metabolic pathways and specificities of glucose catabolism disorders caused by depression? To address the above scientific questions, we creatively combined traditional metabolomics technology with stable isotope-resolved metabolomics to research the glucose catabolism of the corticosterone-induced PC12 cell damage model and the adriamycin-induced glomerular podocyte damage model...

BACKGROUND AND PURPOSE: Osteoarthritis, a major cause of disability in developed countries does not have effective treatment. Activation of TLR4 and innate immune response factors contribute to osteoarthritis progressive cartilage degradation. There are no clinically available TLR4 inhibitors. Interestingly, the antidepressant amitriptyline could block this receptor. Thus, we evaluated amitriptyline anti-TLR4 effects on human osteoarthritis chondrocytes in order to repurpose it as an inhibitor of innate immune response in joint inflammatory pathologies...

Delayed onset of antidepressant action is a shortcoming in depression treatment. Ketamine and its metabolite (2R,6R)-hydroxynorketamine (HNK) have emerged as promising rapid-acting antidepressants. However, their mechanism of action remains unknown. In this study, we first described the anxious and depression-prone inbred mouse strain, DBA/2J, as an animal model to assess the antidepressant-like effects of ketamine and HNK in vivo . To decode the molecular mechanisms mediating HNK's rapid antidepressant effects, a longitudinal cerebrospinal fluid (CSF) proteome profiling of its acute and sustained effects was conducted using an unbiased, hypothesis-free mass spectrometry-based proteomics approach...

Electroacupuncture (EA) is used as an adjunctive treatment for depression. This study was conducted to evaluate the efficacy and mechanisms of EA in the depressive rat model induced by chronic unpredictable mild stress (CUMS) in male adult Wistar rats. The underlying mechanisms were explored by using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis of the proteins in the prefrontal cortex (PFC), and observing the number of the PFC neurons stained with hematoxylin and eosin (H&E) and synaptic morphological changes under transmission electron microscopy (TEM)...

Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. However, the systematic mapping of the interactions between drugs and bacteria has only started recently1 and the main underlying mechanism proposed is the chemical transformation of drugs by microorganisms (biotransformation). Here we investigated the depletion of 15 structurally diverse drugs by 25 representative strains of gut bacteria. This revealed 70 bacteria-drug interactions, 29 of which had not to our knowledge been reported before...