Genome-wide analysis of kainic acid-induced gene expression in dentate gyrus from CTR and SRF knockout mice.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE60772 | GEO | 2015/02/02
SECONDARY ACCESSION(S): PRJNA259539
REPOSITORIES: GEO
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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.
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Project description:Temporal lobe epilepsy (TLE) can develop from alterations in hippocampal structure and circuit characteristics, and can be modeled in mice by administration of kainic acid (KA). Adult neurogenesis in the dentate gyrus (DG) contributes to hippocampal functions and has been reported to contribute to the development of TLE. Some of the phenotypical changes include neural stem and precursor cells (NPSC) apoptosis, shortly after their birth, before they produce hippocampal neurons. Here we explored these early phenotypical changes in the DG 3 days after a systemic injection of KA inducing status epilepticus (KA-SE), in mice. We performed a multi-omics experimental setup and analyzed DG tissue samples using proteomics, transcriptomics and microRNA profiling techniques, detecting the expression of 2327 proteins, 13401 mRNAs and 311 microRNAs. We here present a description of how these data were obtained and make them available for further analysis and validation. Our data may help to further identify and characterize molecular mechanisms involved in the alterations induced shortly after KA-SE in the mouse DG.
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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.
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Project description:The intrahippocampal kainic acid (IHKA) mouse model is an extensively used in vivo model to investigate the pathophysiology of mesial temporal lobe epilepsy (mTLE) and to develop novel therapies for drug-resistant epilepsy. It is characterized by profound hippocampal sclerosis and spontaneously occurring seizures with a major role for the injected damaged hippocampus, but little is known about the excitability of specific subregions. The purpose of this study was to electrophysiologically characterize the excitability of hippocampal subregions in the chronic phase of the induced epilepsy in the IHKA mouse model. We recorded field postsynaptic potentials (fPSPs) after electrical stimulation in the CA1 region and in the dentate gyrus (DG) of hippocampal slices of IHKA and healthy mice using a multielectrode array (MEA). In the DG, a significantly steeper fPSP slope was found, reflecting higher synaptic strength. Population spikes were more prevalent with a larger spatial distribution in the IHKA group, reflecting a higher degree of granule cell output. Only minor differences were found in the CA1 region. These results point to increased neuronal excitability in the DG but not in the CA1 region of the hippocampus of IHKA mice. This method, in which the excitability of hippocampal slices from IHKA mice is investigated using a MEA, can now be further explored as a potential new model to screen for new interventions that can restore DG function and potentially lead to novel therapies for mTLE.
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