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Genome-wide analysis of kainic acid-induced gene expression in dentate gyrus from CTR and SRF knockout mice.

ABSTRACT: To identify genes regulated by SRF in response to increased neuronal activity whole-genome expression profiling (Illumina Mouse WG-6 microarrays) of kainic acid-induced genes were performed. We found that loss of SRF in DG leads to specific deficits in activity-induced gene expression. Identified genes functions are associated with synapse plasticity, epilepsy, outgrowth of neurites, behavior and MAPK signaling pathway.

ORGANISM(S): Mus musculus

PROVIDER: GSE60772 | GEO | 2015/02/02

SECONDARY ACCESSION(S): PRJNA259539

REPOSITORIES: GEO

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Genome-wide analysis of kainic acid-induced gene expression in dentate gyrus from CTR and SRF knockout mice.

Project description:To identify genes regulated by SRF in response to increased neuronal activity whole-genome expression profiling (Illumina Mouse WG-6 microarrays) of kainic acid-induced genes were performed. We found that loss of SRF in DG leads to specific deficits in activity-induced gene expression. Identified genes functions are associated with synapse plasticity, epilepsy, outgrowth of neurites, behavior and MAPK signaling pathway. The microarray experiment was performed to identify SRF-dependent activity-induced genes, using brain-specific, inducible SRF gene knockout mice. Conditional mutants of Srf were obtained by crossing mice in which Srf gene was flanked by loxP sites (Srf f/f) with an CaMKCreERT2 line to ablate its expression exclusively in excitatory forebrain neurons. Knockouts (KO = Srf f/f;CaMKCreERT2) and control littermates (CTR = Srf f/f) were used in the experiments. To enable time-specific induction of SRF deletion, adult mice, were injected with tamoxifen. Global gene expression induced by kainic acid (KA, 35-50 mg/kg) was analyzed. At 6 hours after seizures induction (seizures severity 5; according to modified Racine scale) or saline injection, CTR and KO animals were sacrificed and dentate gyrus was microdissected and used for RNA isolation. In order to identify SRF-regulated genes, we used Illumina MouseWG-6 v2.0 Expression BeadChips.

2015-02-02 | E-GEOD-60772 | biostudies-arrayexpress

ECS-induced gene expression changes in mouse dentate gyrus

Project description:Neuronal activity-dependent gene expression plays important roles in neural plasticity. We use electroconvulsive stimulation (ECS) as an in vivo model for neuronal activation to identify genes that are regulated by neuronal activity. Dentate gyri (DG) were microdissected 4 hours after sham or ECS treatment for gene expression profiling. 4 total samples were analysed (2 for each condition). Averaged expression values between sham and ECS samples were pair-wise compared.

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Multi-omics profile of the mouse dentate gyrus after kainic acid-induced status epilepticus.

Project description: Not available

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Single-cell transcriptome of commissural and non-commissural dentate gyrus granule cells

Project description:Dentate granule cells (GCs) have been characterized as unilaterally projecting neurons within each hippocampus. Using anterograde and retrograde labeling, we identified a unique class, the commissural GCs, which atypically project to the contralateral hippocampus in mice. This data set includes single-cell mRNA sequencing reads from retrogradely-labeled (commmissural) and -non-labeled (non-commissural) GCs from control mice and from mice treated with unilateral intrahippocampal kainic acid microinjections (70 nl, 5 mM; cells were collected two weeks after microinjection); control mice were treated with unilateral intrahippocampal saline microinjections (equal amount to kainic acid; cells were collected two weeks after microinjection). These experiments were performed in adult (2.5-3.5 months old) Rbp4-Cre transgenic mice.

2023-04-26 | GSE214905 | GEO

iTRAQ-based proteomic analysis of dentate gyrus in temporal lobe epilepsy with hippocampal sclerosis

Project description:Temporal lobe epilepsy (TLE) is the most frequent type of focal epilepsy in adults, typically resistant to pharmacological treatment and mostly present with cognitive impairment and psychiatric comorbidities. The most common neuropathological hallmark in TLE patients is hippocampal sclerosis(HS). However, the underlying molecular mechanisms involved remain poorly characterized. Dentate gyrus(DG), one specific hippocampal subarea, structural and functional changes imply a key involvement of the DG in the development of TLE. In this study, isobaric tags for relative and absolute quantitation (iTRAQ) -based quantitative proteomic technique was performed to analysis of hippocampal DG obtained from patients with TLE-HS compared to control samples obtained from the autopsy. Our proteomic data identified 5583 proteins, of which 82 proteins were up-regulated and 90 proteins were down-regulated. Bioinformatics analysis indicated that differential expressed proteins enriched in “synaptic vesicle”, “mitochondrion”, “cell-cell adhesion”, “regulation of synaptic plasticity”, “ATP binding” and “Oxidative phosphorylation”. Protein-protein interaction network analysis found a pivotal module of 10 proteins that relate to “Oxidative phosphorylation”. This study is the first to investigate proteomic alterations in DG region of TLE-HS patients, and pave the way to better understanding of epileptogenesis mechanisms and future therapeutic intervention.

2021-01-18 | PXD023048 | Pride

Sox11 - a novel activity-regulated gene with dentate gyrus-specific expression

Project description:Neuronal activity initiates transcriptional programs that shape long-term changes in plasticity. Although neuron subtypes differ in their plasticity response, most activity-dependent transcription factors are broadly expressed across different neuron subtypes and brain regions. Thus, how regional and neuronal subtype-specific plasticity are established on the transcriptional level remains poorly understood. Here, we report that the developmental transcription factor Sox11 is induced in mature neurons upon hippocampal circuit activity and that this activity-dependent expression occurs exclusively in the dentate gyrus (DG) of the hippocampus. In addition, we show that Sox11 can modify synaptic plasticity and intrinsic excitability of DG granule cell neurons as well as the expression of plasticity-related genes. We propose that Sox11 is a DG-specific activity-dependent gene and might play a role in fine tuning regional plasticity in the hippocampal circuit.

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ECS-induced gene expression changes in mouse dentate gyrus

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Whole transcriptome analysis of postmortem human hippocampus dentate gyrus granlule cells

Project description:We investigated the transcriptome of dentate gyrus (DG) granule cells in postmortem hippocampus from 79 subjects with mental illness (schizophrenia, bipolar disorder, major depression) or non-psychiatric controls.

2014-04-09 | GSE42546 | GEO

Extrinsic factors facilitate neurogenesis in a human induced pluripotent stem cell-derived model of the dentate gyrus

Project description:Modeling development and maturation of the human hippocampus in culture is crucial to elucidate the physiological and pathological mechanisms of its neurogenesis. We established human hippocampal cell cultures by means of controlled neuralization of human induced pluripotent stem cells (hiPSCs). The timely re-activation of WNT signaling in hiPSCs, which were previously driven toward a dorsal telencephalic identity by the combined inhibition of WNT, BMP and TGF-β signaling, produced neural progenitors with a gene expression signature typical of human embryonic dentate gyrus (DG) cells. Key markers of neurogenesis resulted downstream of the NOTCH and WNT pathway and were upregulated in these progenitors. Notably, we found that, in addition to continuous WNT signaling, a specific laminin isoform is crucial to prolonging DG stem state and to extend DG progenitor proliferation for over 200 days in vitro. In fact, transition from laminin 511 to mouse laminin inhibited cell proliferation and promoted the differentiation of DG cells. Interestingly, global gene expression profiles of early and late progenitor cells and neurons suggest that a niche of laminin 511 and WNT signaling is sufficient to maintain a cell population enriched in DG progenitor cells and neurons. Finally, the xenograft of human DG progenitors into the DG of adult immunosuppressed host mice produced efficient integration of neurons, which innervated CA3 layer cells with an area covered by synapses similar to the area covered by endogenous hippocampal neuron synapses. Our observations indicate that neurons produced in the established culture niche resemble bona-fide human DG neurons.

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Effect of methanol fixation on single cell RNA sequencing of the murine dentate gyrus.

Project description:We evaluated the effect of methanol (MeOH) fixation on adult murine dentate gyrus (DG) single cell suspensions.

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