The role microglia in electroconvulsive threapy (ECT) in depressed-like mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA507273 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Recent studies implicate microglia alterations in the pathogenesis and pathophysiology of depression. For example, chronic unpredictable stress (CUS) in mice can cause degeneration of microglia and depressive-like symptoms, which can be reversed by microglia stimulating drugs. To further test the causal role of microglia in CUS-induced depression and its reversal by an anti-depressive procedure, we examined the effects of microglia depletion with the CSF-1 antagonist PLX5622 or pharmacological blockade of microglial activation with minocycline on normal mood-related behavior, CUS-induced depressive-like symptoms, and the amelioration of these symptoms by electroconvulsive treatment (ECT). We report that microglia-depleted mice showed no depression, anxiety or spatial memory disturbances. Microglia depletion had no effect on the development of CUS-induced depressive-like symptoms and suppressed neurogenesis, but it completely abrogated the beneficial effects of ECT on depression and neurogenesis, as well as on the all ECT-induced transcriptomic changes. ECT induced several morphological changes in microglia, suggestive of increased activation status, and blockade of this activation by minocycline attenuated the anti-depressive and pro-neurogenesis effect of ECT and reduced the number of contacts between microglia and neurogenic cells. The immune checkpoint gene Lag3, whose expression by microglia was increased following CUS, was the only microglial transcript significantly reduced by ECT. Furthermore, treatment of depressed-like mice with a LAG3 monoclonal antibody was further tested.
2021-01-01 | GSE123027 | GEO
Project description:Neurostimulation by electroconvulsive therapy is highly effective in neuropsychiatric disorders by an unknown mechanism. Microglial toxicity plays a key role in chronic neuro-inflammatory brain diseases, where there is critical shortage in therapies. To investigate the direct effect of electroconvulsive seizures (ECS) on the CNS innate immune system, we performed transcriptome analysis on spinal microglia from ECS- and sham-treated naïve mice.
2022-09-01 | GSE137184 | GEO
Project description:We demonstrated that the offspring of depressed fathers display reduced resilience to stress and enhanced susceptibility to depression. To explain the observed behavioural phenotypes of depression in offspring produced by depressed fathers, molecular profiling was performed in key brain regions.We examined the hippocampal sample from normal male mice, stress induced depressive male mice and male offspring born to stress-induced depressed male mice by RNA sequencing.
2020-06-28 | GSE133494 | GEO
Project description:Purpose: We purified whole brain microglia of MFP2 knockout mice and control mice utilizing percoll gradient and FACS sorting, followed by microarray analysis to define the molecular changes in MFP2 knockout mice at the endstage of the disease. We compared the microglia transcriptome of Mfp2-/- microglia to that of SOD1-G93A microglia isolated from spinal cord to define the microglia signature associated with a non-neurodegenerative environment. Results and conclusions: Mfp2-/- microglia acquire an activation state characterized by activation of mammalian target of rapamycin (mTOR). In addition, activated microglia display reduced expression of genes that are normally highly expressed by surveillant microglia in steady-state conditions. The immunological profile of is heterogeneous and encompasses upregulation of both pro- and anti-inflammatory genes. In contrast to the neurodegeneration-specific microglia profile in SOD1-G93A mice, Mfp2-/- microglia do not induce genes associated with phagocytosis, lysosomal activation and neurotoxicity. 4 MFP2 knockout and 4 control samples were subjected to microarray analysis.
2015-04-14 | E-GEOD-66420 | biostudies-arrayexpress
Project description:Microglia are tissue macrophages of the central nervous system (CNS) that control tissue homeostasis, and as such they are crucially important for organ integrity. Microglia dysregulation is thought to be causal for a group of neuropsychiatric, neurodegenerative and neuroinflammatory diseases, called ‘microgliopathies’. However, how the intracellular stimulation machinery in microglia is controlled is poorly understood. By using expression studies, we identified the ubiquitin-specific protease (Usp) 18 in white matter microglia that essentially contributes to microglial quiescence under homeostatic conditions. We further found that microglial Usp18 negatively regulated the activation of STAT1 and concomitant induction of interferon-induced genes thereby disabling the termination of IFN signalling. Unexpectedly, the Usp18-mediated feedback loop was independent from the catalytic domain of the protease but instead required the interacting region of Ifnar2. Additionally, the absence of Ifnar1 completely rescued microglial activation indicating a tonic IFN signal mediated by receptor interactions under non-diseased conditions. Finally, conditional depletion of Usp18 only in myeloid cells significantly enhanced the disease burden in a mouse model of CNS autoimmunity, increased axonal and myelin damage and determined the spatial distributions of CNS lesions that shared the same STAT1 signature as myeloid cells found in active multiple sclerosis (MS) lesions. These results identify Usp18 as novel negative regulator of microglia activation, demonstrate a protective role of the IFNAR pathway for microglia and establish Usp18 as potential therapeutic target for the treatment of MS. Primary microglia (WT, USP18ko and USP18_C61A mice) and BV-2 cells (treated with control siRNA or siRNA against USP18) were incubated with 500 U/ml IFN-b. At different timepoints (0h, 6h, and 24h) RNA samples were taken and analyzed via Microarray
2015-04-20 | E-GEOD-61500 | biostudies-arrayexpress
Project description:To elucidate differential gene expression pattern in atopic diathesis model mice spinal cord microglia compared to normal mice. Sort microglia from atopic diathesis model mice and control mice, extract RNA and subjected to RNA array assay.
2015-07-09 | E-GEOD-68202 | biostudies-arrayexpress
Project description:We demonstrated that DNMT3a was decreased at E3.5 to E6.5 stage in embryos developing from zygotes injected with sperm sRNAs from depressed mice.To uncover the consequence caused by DNMT3a transient reduction in developing embryos, we injected sperm sRNAs from normal or depressed mice into zygotes and systematically profiled the DNA methylome of embryos at E4.5 stage (sRNA-Dep-E4.5 vs sRNA-Ctl-E4.5) by single-cell level whole genome bisulphite sequencing (SC-WGBS).
2020-06-28 | GSE133496 | GEO
Project description:Cystain B (Cstb) is a ubiquitously expressed cysteine protease inhibitor and mutations of the CSTB gene lead to the neurodegenerative disease progressive myoclonus epilepsy of Unverricht-Lundorg type (EPM1). We are interested in the microglia-specific, Cstb-dependent gene-expression changes in mice and in this data set, we include gene-level expression data from cultured primary microglia of control and Cstb-/- mice extracted from neonatal mice at P5 and we identified 156 differentially-expressed genes in Cstb-/- microglia. We analyzed 8 samples in total and we compared 4 control microglia samples to 4 Cstb-/- microglia samples. Genes with a fold change > 1.3 and with p < 0.05 in T-test with BH correction were considered differentially expressed.
2016-06-29 | E-GEOD-64823 | biostudies-arrayexpress
Project description:Microglia are the resident macrophages of the central nervous system (CNS). Gene profiling identified the transcriptional regulator Sall1 as a microglia signature gene. Given the high expression of Sall1 in microglia, we sought to identify its function in vivo. The Sall1CreER allele has been targeted into the Sall1 locus, therefore Sall1CreER/fl mice (heterozygous for both alleles) allow inducible ablation of Sall1 expression in microglia after tamoxifen treatment. We performed RNA-seq to examine gene expression profiles of microglia sorted from tamoxifen treated adult Sall1CreER/fl mice and Sall1fl/fl control littermates. Microglia were obtained with > 98% purity and the absence of Sall1 was confirmed in Sall1CreER/fl microglia. We could show that deletion of Sall1 in microglia in vivo resulted in the conversion of these cells from resting tissue macrophages into inflammatory phagocytes leading to altered neurogenesis and disturbed tissue homeostasis. Similar changes in gene expression profiles were found in Sall1-deficient microglia isolated from tamoxifen-treated Cx3cr1CreERSall1fl/fl mice. In these mice, deletion of Sall1 is targeted to CX3CR1+ myeloid cells including microglia and CNS-associated macrophages but not to any other CNS-resident cells. This indicated that Sall1 transcriptional regulation maintains microglia identity and physiological properties in the CNS.
2016-10-19 | E-MTAB-5077 | biostudies-arrayexpress
Project description:This data set shows dramatic changes in gene expression in microglia isolated from C57Bl6/J mice subjected to transient middle cerebral artery occlusion, as compared to those subjected to sham surgery. Mice deficient in Mincle (Clec4e-/-) showed significantly improved injury outcomes 3 and 7 days after transient middle cerebral artery occlusion. However, when comparing changes in gene expression in microglia 24 hours after blood reperfusion, there were no differences between wild-type and Clec4e-/- mice, indicating that Mincle does not participate in early microglial activation. Wild type and Mincle knock-out (Clec4e-/-) mice. After 1 h of transient middle cerebral artery occlusion (tMCAO) and 24 h of reperfusion, mice were perfused with PBS, their brains dissected, and 2 ipsilesional hemispheres (with cerebellum and brainstem removed) pooled for microglia isolation. For sham-operated animals, the whole forebrain was used and brains were not pooled. After myelin separation by Percoll gradient centrifugation, around 80,000 CD45intermediate, CD11b+ microglial cells were sorted from each sample. Sham samples n=3, tMCAO samples n=5.
2016-03-24 | E-GEOD-77986 | biostudies-arrayexpress