Metabolomic profiling relates tianeptine effectiveness with hippocampal GABA, myo-inositol, cholesterol, and fatty acid metabolism restoration in socially isolated rats.

Rationale: Discovering biomarkers of major depressive disorder (MDD) can give a deeper understanding of this mood disorder and improve the ability to screen for, diagnose, and treat MDD.

Objectives: In this study, metabolomics was used in unraveling metabolite fluctuations of MDD and drug outcome by creating specific metabolomic fingerprints. We report metabolomic patterns of change of the hippocampus of adult male Wistar rats following chronic social isolation (CSIS) (6 weeks), an animal model of depression, and/or chronic tianeptine (Tian) treatment (10 mg kg per day) (lasting 3 weeks of 6-week CSIS), monitored by using comprehensive GC × GC-MS.

Predictive semiology of psychogenic non-epileptic seizures in an epilepsy monitoring unit.

Introduction: The diagnosis of psychogenic nonepileptic seizures (PNES) is a common clinical dilemma. We sought to assess the diagnostic value of four ictal signs commonly used in differentiating PNES from epileptic seizures (ES).

Methods: We retrospectively reviewed consecutive adult video-electroencephalogram (VEM) studies conducted at a single tertiary epilepsy center between May 2009 and August 2016.

Tianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats.

Deregulation of synaptic function and neurotransmission has been linked with the development of major depression disorder (MDD). Tianeptine (Tian) has been used as antidepressant with anxiolytic properties and recently as a nootropic to improve cognitive performance, but its mechanism of action is unknown. We conducted a proteomic study on the hippocampal synaptosomal fractions of adult male Wistar rats exposed to chronic social isolation (CSIS, 6 weeks), an animal model of depression and after chronic Tian treatment in controls (nootropic effect) and CSIS-exposed rats (lasting 3 weeks of 6-week CSIS) (therapeutic effect).

Fluoxetine exerts subregion/layer specific effects on parvalbumin/GAD67 protein expression in the dorsal hippocampus of male rats showing social isolation-induced depressive-like behaviour.

The molecular background of depression is intensively studied in terms of alterations of inhibitory circuits, mediated by gamma aminobutyric acid (GABA) signalization. We investigated the effects of chronic social isolation (CSIS) and chronic fluoxetine (Flx) treatment (15 mg/kg/day) (3 weeks), on Parvalbumin (PV) and GAD67 expression in a layer-specific manner in rat dorsal hippocampal subregions. CSIS-induced depressive- and anxiety-like behaviours were confirmed with decrease in sucrose preference and increase in marble burying during behavioural testing, while Flx antagonized these effects.

Hippocampal synaptoproteomic changes of susceptibility and resilience of male rats to chronic social isolation.

The susceptibility of an individual to chronic social isolation (CSIS) stress may cause major depression (MD) whereby some individuals are resistant to the stress. Recent studies relate MD with altered expression of synaptic proteins in specific brain regions. To explore the neurobiological underpinnings and identify candidate biomarkers of susceptibility or resilience to CSIS, a comparative proteomic approach was used to map hippocampal synaptic protein alterations of rats exposed to 6 weeks of CSIS, an animal model of depression.

Tianeptine Enhances Energy-related Processes in the Hippocampal Non-synaptic Mitochondria in a Rat Model of Depression.

Tianeptine (Tian) has been widely used in treating mood and anxiety disorders, and recently as a nootropic to improve cognitive performance. However, its mechanisms of action are insufficiently clear. We used a comparative proteomic approach to identify sub-proteome changes in hippocampal cytosol and non-synaptic mitochondria (NSM) following chronic Tian treatment (3 weeks, 10 mg/kg/day) of adult male Wistar rats and rats exposed to chronic social isolation stress (CSIS) (6 weeks), an animal model of depression.

Fluoxetine modulates neuronal activity in stress-related limbic areas of adult rats subjected to the chronic social isolation.

Antidepressant fluoxetine (Flx) is the first therapeutic choice for the treatment of major depression (MD), however neuroanatomical spots of its action remain unclear. Immunohistochemical detection of c-Fos protein expression has been used for mapping activated neuronal circuits upon various stressors and drugs. We investigated the effect of 3 weeks of Flx treatment (15 mg/kg/day) on changes in neuronal activity, by mapping the number of c-Fos cells, in several brain subregions in adult male rats of control and following 3 weeks of chronic social isolation (CSIS), an animal model of depression.

Social isolation stress-resilient rats reveal energy shift from glycolysis to oxidative phosphorylation in hippocampal nonsynaptic mitochondria.

Aims: To examine the differences in the hippocampal proteome profiles of resilience or susceptibility to chronic social isolation (CSIS), animal model of depression, and to identify biomarkers that can distinguish the two.

Main Methods: Comparative subproteomic approach was used to identify changes in hippocampal cytosol and nonsynaptic mitochondria (NSM) of CSIS-resilient compared to CSIS-sensitive or control rats. The resilient and sensitive phenotypes of CSIS rats were distinguished based on their sucrose preference values.

Clozapine increased c-Fos protein expression in several brain subregions of socially isolated rats.

Chronic social stress and/or pharmacological treatments differentially modulate the expression of c-Fos, a marker of neuronal activity, in subregions of the rat brain. Here, we examined the effect of the atypical antipsychotic Clozapine (Clz) (20 mg/kg/day for 3 weeks) on the neuronal activation pattern of c-Fos protein expression in stress-relevant brain subregions of adult male Wistar rats exposed to chronic social isolation (CSIS: 3 weeks), an animal model of depression and schizophrenia, and controls. The protein expression of c-Fos was also used to map neuronal populations in brain subregions activated by CSIS alone.

Brain Sub/Region-Specific Effects of Olanzapine on c-Fos Expression of Chronically Socially Isolated Rats.

Olanzapine (Olz) is an atypical antipsychotic used to treat depression, anxiety and schizophrenia, which can be caused by chronic psychosocial stress. c-Fos protein expression has been used as an indirect marker of neuronal activity in response to various forms of stress or pharmacological treatments. We examined the effects of a 3-week treatment of Olz (7.

Tianeptine antagonizes the reduction of PV+ and GAD67 cells number in dorsal hippocampus of socially isolated rats.

Adult male rats exposed to chronic social isolation (CSIS) show depressive- and anxiety-like behaviors and reduce the numbers of parvalbumin-positive (PV+) interneurons in the dorsal hippocampus. We aimed to determine whether tianeptine (Tian), administered during the last three weeks of a six-week-social isolation (10 mg/kg/day), may reverse CSIS-induced behavioral changes and antagonize the CSIS-induced reduction in the number of PV+ interneurons. We also studied whether Tian affects the GABA-producing enzyme GAD67+ cells, in Stratum Oriens (SO), Stratum Pyramidale (SP), Stratum Radiatum (SR) and Stratum Lacunosum Moleculare (LM) of CA1-3, as well as in molecular layer-granule cell layer (ML-GCL) and Hilus (H) of the dentate gyrus (DG).

Proteomic characterization of hippocampus of chronically socially isolated rats treated with fluoxetine: Depression-like behaviour and fluoxetine mechanism of action.

Due to the severity of depressive symptoms, there remains a necessity in defining the underlying mechanisms of depression and the precise actions of antidepressants in alleviating these symptoms. Proteomics is a powerful and promising tool for discovering novel pathways of cellular responses to disease and treatment. As chronic social isolation (CSIS) is a valuable animal model for studying depression, we performed a comparative subproteomic study of rat hippocampus to explore the effect of six weeks of CSIS and the therapeutic effect of chronic fluoxetine (Flx) treatment (last three weeks of CSIS; 15 mg/kg/day).

Chronic Treatment with Fluoxetine or Clozapine of Socially Isolated Rats Prevents Subsector-Specific Reduction of Parvalbumin Immunoreactive Cells in the Hippocampus.

The dysfunction of parvalbumin-positive (PV+) interneurons, the most abundant type of hippocampal GABAergic inhibitory interneuron, has been implicated in mood disorders. We recently reported that adult male Wistar rats exposed to three weeks of social isolation show depressive- and anxiety-like behaviors and a reduced number of PV+ interneurons in all hippocampal subregions. As GABA neurotransmission has been proposed as a potential therapeutic target of antidepressant and antipsychotic medications, we examined whether treatment with the antidepressant fluoxetine (Flx) (15 mg/kg/day) or the antipsychotic clozapine (Clz) (20 mg/kg/day) during three weeks of social isolation in rats offered protection from the isolation stress-induced reduction in the number of PV+ interneurons in hippocampal subregions.

Fluoxetine reverses behavior changes in socially isolated rats: role of the hippocampal GSH-dependent defense system and proinflammatory cytokines.

Exposure of an organism to chronic social isolation (CSIS) has been shown to have an important role in depression. Fluoxetine (Flx) is a first-line treatment for depression; however, its downstream mechanisms of action beyond serotonergic signaling remain ill-defined. We investigated the effect of 3 weeks of Flx (15 mg/kg/day) treatment on behavioral changes and protein expression/activity of the GSH-dependent defense system, including reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GLR), and glutathione S-transferase (GST), as well as catalase (CAT), in the hippocampus of rats exposed to 6 weeks of CSIS.

Olanzapine alleviates oxidative stress in the liver of socially isolated rats.

Olanzapine, an antipsychotic drug, is used to treat depressive disorder, but its effects on the liver, the main site of drug metabolism, still remain elusive. We studied the effects of 3 weeks of olanzapine treatment (7.5 mg/kg per day) on the malondialdehyde (MDA) and protein carbonyl (PCO) contents, protein expression of copper/zinc superoxide dismutase (CuZnSOD), and activity of total superoxide dismutase (SOD), as well as catalase (CAT) protein expression and activity levels in the liver cytosol of rats exposed to 6 weeks of chronic social isolation (CSIS), which causes depressive- and anxiety-like behaviors.

Chronic fluoxetine treatment directs energy metabolism towards the citric acid cycle and oxidative phosphorylation in rat hippocampal nonsynaptic mitochondria.

Fluoxetine (Flx) is the principal treatment for depression; however, the precise mechanisms of its actions remain elusive. Our aim was to identify protein expression changes within rat hippocampus regulated by chronic Flx treatment versus vehicle-controls using proteomics. Fluoxetine-hydrohloride (15mg/kg) was administered daily to adult male Wistar rats for 3weeks, and cytosolic and nonsynaptic mitochondrial hippocampal proteomes were analyzed.