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: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 whole blood (WB) 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 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: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:Gene expression profiling of blood cells in patients with major depressive disorder (MDD) has been used to identify potential biomarkers and to address the pathophysiology of MDD. However, whether alteration in gene expression in blood cells are reflected in the brain of the same individual is unclear. Here, we used an animal model of depression to investigate intra-subject correlation of gene expression patterns between the whole blood (WB) and the medial prefrontal cortex (mPFC). Ovariectomized mice exposed to the chronic mild stress were used as an animal model of depression.
Project description:Prenatal stress is one of the risk factors for the development of mental disorders in offspring, but its underlying mechanism remains elusive. To perform epigenomic profiling of prenatal stress effects on fetal brains, ATAC-seq and RNA-seq were used to explore the changes of chromatin accessibility and gene expression on embryonic brains at E15.5 of offspring from pregnant mice, which were exposed to chronic mild unpredictable stress between E5.5 to E14.5.
Project description:Gene expression profiling of blood cells in patients with major depressive disorder (MDD) has been used to identify potential biomarkers and to address the pathophysiology of MDD. However, whether alteration in gene expression in blood cells are reflected in the brain of the same individual is unclear. Here, we used an animal model of depression to investigate intra-subject correlation of gene expression patterns between the whole blood (WB) and the medial prefrontal cortex (mPFC). Ovariectomized mice exposed to the chronic ultra-mild stress were used as an animal model of depression. The major findings of the current genome-wide microarray analysis are that 1) the expression levels of 467 genes that were expressed in both tissues correlated positively between the two tissues, 2) alterations in the expression of 4,215 genes in the WB of OVX-operated mice compared to the sham-operated mice were concordant with alterations in the corresponding mPFC, 3) the biological terms over-represented in the 4,215 OVX-affected genes were associated with ribosomal function, and 4) the 6 genes that are potentially relevant to depression-like behavior were observed to be differentially expressed in the WB of the model mice. The current findings suggest that alterations in the expression of a subset of genes are significantly correlated between the WB and the mPFC with in the same individual in an experimental model of depression. Female mice were subjected to chronic ultra-mild stress, a bilateral ovariectomy, or both. Sham-operated mice without stress were used as the control. Medial prefrontal cortex and whole blood were obtained from the same individual (n = 6 in each group), and analyzed using an Agilent SurePrint G3 Mouse GE 8×60K Microarray (Design ID: 028005)
Project description:Translational profiling of cortical layer5a neurons in response to stress and normalization by SSRI, Fluoxetine (Flx). Some Flx-treated animals were anxious.