ABSTRACT: Transcription profiling of dentate gyrus and anterior cingulate cortex in mice exposed Unpredicatble Chronic Mild Stress and treated with fluoxetine
Project description:Groups of 8 adult BALB/c male mice were either untreated or exposed for 9 weeks to unpredicatble chronic mild stress (UCMS), or exposed for 7 weeks to UCMS and treated for the last 5 weeks with fluoxetine (Flx) diluted in drinking water, or untreated for 2 weeks and received Flx for 5 weeks. Total RNAs from dentate gyrus (DG) and anterior cingulate cortex (ACC) were profiled after hybridization with Agilent SurePrint G3 Mouse GE 8x60K Microarray v1 to identify transcriptional biomarkers of major depression.
Project description:Transcription profiling of blood, dentate gyrus and anterior cingulate cortex in mice exposed Unpredicatble Chronic Mild Stress and treated with fluoxetine
Project description:Major depression is a multidimensional disorder highly prevalent in modern society. Although several classes of antidepressants (ADs) are currently available to treat depression, the effectiveness of treatment is still limited, as many patients do not show full remission; thus, there is a need to find better patients’ directed therapeutic strategies. Neuroplastic changes in several brain regions, namely in the hippocampal dentate gyrus (DG), are amongst the best correlates of depression and of ADs actions. In this study the targets and molecular mediators of chronic stress and of four ADs from different pharmacological classes (fluoxetine, imipramine, tianeptine and agomelatine) were investigated in the DG. Using the unpredictable chronic mild stress (uCMS) animal model of depression, the molecular commonalities and specificities of the ADs were determined. All ADs, except agomelatine, could reverse the behavioral deficits produced by uCMS, and the neuroplastic changes in the DG; agomelatine reversed only the anhedonic profile in the sucrose consumption test. Chronic stress induced mild but relevant molecular changes that were mostly reversed by fluoxetine, imipramine and tianeptine. Fluoxetine reduced pro-inflammatory response and increased cell metabolism pathways. Its actions were mostly dependent on molecular changes occurring in neurons. Similarities were found between imipramine and tianeptine molecular actions and targets, as both activated pathways related to cellular protection. Moreover, no particular neural cell type enrichment was found with both treatments. Agomelatine presented a very dissimilar molecular pattern impacting greatly on Rho-GTPases-related pathways in oligodendrocytes and neurons. The recognition of these molecular alterations contributes to the understanding of the processes implicated in the onset and treatment of depression and may pave the way for more effective therapeutic interventions. We compared gene expresssion in the dentate gyros of rats which were either untreated, exposed to unpredictable chronic mild stress, or exposed to the same stress and treated with either fluoxetine, imipramine, tianeptine, or agomelatine
Project description:The gene expression patterns in the dentate gyrus of wild-type mice treated with fluoxetine (15 mg/kg/day for 3 weeks) or vehicle were examined using Affymetrix GeneChip arrays.
Project description:Layer II stellate neurons (entorhinal cortex) and layer III cortical neurons (hippocampus CA1, middle temporal gyrus, posterior cingulate, superior frontal gyrus, primary visual cortex) were gene expression profiled. Brain regions are from individuals who had been diagnosed with mild cognitive impairment. Experiment Overall Design: ~500 neurons were selected from each of 6 brain regions. Total RNA was isolated from each batch of neurons, double round amplified, and hybridized to Affymetrix Human Genome U133 Plus 2.0 arrays.
Project description:Layer II stellate neurons (entorhinal cortex) and layer III cortical neurons (hippocampus CA1, middle temporal gyrus, posterior cingulate, superior frontal gyrus, primary visual cortex) were gene expression profiled. Brain regions are from non-demented individuals with intermediate Alzheimer's disease neuropathologies Keywords: neuronal gene expression profiling
Project description:We carried out untargeted metabolomics of the prefrontal cortex of rats exposed to chronic social isolation (CSIS), a rat model of depression, and/or fluoxetine treatment using liquid chromatography-high resolution mass spectrometry.
Project description:Gene expression was measured from the dentate gyrus and entorhinal cortex harvested from human postmortem samples. We harvested the dentate gyrus DG from healthy human brains ranging from 33 to 88 years of age. Additionally, from each brain we harvested the entorhinal cortex (EC) as a within-brain control. Using Affymetrix microarray chips we generated gene-expression profiles of each individual tissue samples. DG expression levels were first normalized against the EC, and the normalized DG transcripts were then correlated against age.
Project description:Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder. Several studies have attempted to characterize molecular alterations associated with PTSD, but most findings were limited to the investigation of specific cellular markers in the periphery or defined brain regions. In the current study, we aimed to unravel affected molecular pathways/mechanisms in the fear circuitry associated with PTSD. We interrogated a foot shock induced-PTSD mouse model by integrating proteomics and metabolomics profiling data. Alterations at the proteome level were analyzed using in vivo 15N metabolic labeling combined with mass spectrometry in prelimbic cortex (PrL), anterior cingulate cortex (ACC), basolateral amygdala (BLA), central nucleus of amygdala (CeA) and CA1 of hippocampus between shocked and non-shocked (control) mice, with and without fluoxetine treatment.
Project description:Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder. Several studies have attempted to characterize molecular alterations associated with PTSD, but most findings were limited to the investigation of specific cellular markers in the periphery or defined brain regions. In the current study, we aimed to unravel affected molecular pathways/mechanisms in the fear circuitry associated with PTSD. We interrogated a foot shock induced-PTSD mouse model by integrating proteomics and metabolomics profiling data. Alterations at the proteome level were analyzed using in vivo 15N metabolic labeling combined with mass spectrometry in prelimbic cortex (PrL), anterior cingulate cortex (ACC), basolateral amygdala (BLA), central nucleus of amygdala (CeA) and CA1 of hippocampus between shocked and non-shocked (control) mice, with and without fluoxetine treatment.
