Molecular profiles of cognitive aging
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Scott Small
PROVIDER: E-GEOD-46193 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
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 systemic KA administration to mice. Our specific aim was to understand the molecular mechanisms underlying altered apoptosis levels in NSPC following KA-induced status epilepticus (KA-SE). Accordingly, we chose a multi-omics experimental setup and analyzed DG tissue samples using proteomics, transcriptomics and microRNA profiling techniques. We here present a description of how these date were obtained and provide them to others for further analysis and validation. This may help to further identify and characterize molecular mechanisms involved in the alterations induced shortly after KA-SE in the mouse DG. Total RNA obtained from dentate gyrus 72h after mice were subjected to repeated low dose kainic acid induced status epilepticus or saline i.p. injections
2016-03-12 | E-GEOD-79131 | biostudies-arrayexpress
Project description:We examined the genetic profile of postmortem brain (hippocampal) samples; 15 brains from patients diagnosed with MDD were matched to brains from healthy subjects based on gender, race and age. Gene expression profiles in the dentate gyrus and CA1 subregions of the hippocampus were assessed by cDNA hybridization to 48K human HEEBO whole genome microarrays (Microarray, Inc). Two-group comparison: MDD (13 male, 8 female) vs. Control (11 male, 7 female). Dentate Gyrus (DG): 15 pairs of samples (1 array per pair); CA1: 15 pairs of samples (1 array per pair). Biological replicates. We can not provide a list of normalized values for each individual hybridization (per chip), but rather have a list of average expression values for all hybridizations used in the experiment (n=15). See supplementary files below. CODES: AAm, African American; C, Caucasian; CO, carbon monoxide; CVD, cardiovascular disease; ETOH, ethanol; F, female; Hx, history of alcohol abuse but not currently active; M, male; MDD, Major Depressive disorder, ND, no psychotropic medication detected; NOS, not otherwise specified, OD, drug overdose; PE, prior episode of major depression with psychotic features; PMI, postmortem interval (hours); SIGSW, self-inflicted gunshot wound; [1], Psychotrophic prescriptions within last month; [2], MDD in remission; [3], prescriptions for six days prior to death; *, samples present only in array sets for the dentate gyrus; **, samples present only in array sets for CA1.
2010-10-17 | E-GEOD-24095 | biostudies-arrayexpress
Project description:In vivo high frequency stimulated of left dentate gyrus was performed on anaesthetised rats followed by RNA-seq to study long-term potentiation. Both left and right dentate gyrus was collected, sequenced and compared against each other for naive rats and for rats 30 min, 2 hours, and 5 hours post-HFS.
2015-10-20 | E-MTAB-3375 | biostudies-arrayexpress
Project description:Analysis of the dentate gyrus of amygdala electrical stimulation model of temporal lobe epilepsy. Results provide insight into the molecular mechanism underlying epileptogenesis. This study was designed to estimate changes in gene expression levels after 7 and 30 days after electrical stimulation of amygdala as a model of temporal lobe epilepsy. The advantage of this study is time matched control (sham operated animals sacrificed at the same age as stimulated animals).
2013-08-14 | E-GEOD-49849 | biostudies-arrayexpress
Project description:Background Semantic dementia (SD) is a subtype of frontotemporal dementia (FTD) characterized by language deficits due to severe temporal lobe degeneration. The consistent neuropathological diagnosis is FTD-TDP subtype C, with characteristic round TDP-43 protein inclusions in the dentate gyrus. Despite this striking clinicopathological concordance, the pathogenic mechanisms are largely unexplained forestalling the development of targeted therapeutics. Methods We carried out laser capture microdissection of the dentate gyrus of 15 SD patients and 17 non-demented controls, and assessed relative protein abundance changes by label-free quantitative mass spectrometry. To identify SD specific proteins, we compared our results to eight other FTD and Alzheimer’s disease (AD) proteomic datasets of cortical brain tissue, parallel with functional enrichment analyses and protein-protein interactions (PPI). Results Of the total 5,354 quantified proteins, 151 showed differential abundance (FDR<1%) in SD patients. Seventy-two proteins were previously found altered with the same directional change in at least one FTD/AD proteomic study, while 79 proteins were considered as showing potentially SD specific dysregulation. Functional enrichment indicated an overrepresentation of pathways related to the immune response, metabolic processes, and cell-junction assembly. PPI analysis highlighted a cluster of interacting proteins associated with adherens junction and cadherin binding– the cadherin-catenin complex. Multiple proteins in this complex showed strong and apparent specific upregulation in SD, including β-catenin (CTNNB1), γ-catenin (JUP), and N-cadherin (CDH2). Conclusions We discovered an increase of cell adhesion proteins in SD specifically constituting the cadherin-catenin complex at the synaptic membrane, essential for synaptic signaling. Although further validation is warranted, we anticipate that these findings will help unravel the disease processes underlying SD.
2023-03-10 | PXD033060 | Pride
Project description:The dentate gyrus (DG) of the hippocampus is one of major targets for antidepressant treatments. Our recent research has revealed that selective serotonin reuptake inhibitor (SSRI) treatment causes a long-lasting change in the phenotypes of mature dentate granule neurons to immature state in adult mouse DG. However, it is unknown whether this M-bM-^@M-^\dematurationM-bM-^@M-^] of DG is a common effect of antidepressant treatments and what mechanisms underlie it. Using electroconvulsive stimulation (ECS), a model of highly effective and fast-acting antidepressant therapy, here we show that neural stimulation via ECS induces rapid and lasting dematuration of granule neurons in DG. A single or few times of stimulation transiently reduced mature marker expression and mature synaptic functions. Repetitive stimulation converted this transient dematuration into a stable form lasting more than 1 month. Dematured granule neurons showed higher excitability, and an increase in GABA-mediated inhibition by the benzodiazepine diazepam prevented the lasting maintenance phase of dematuration without affecting the initial induction phase. Our study suggests that dematuration of DG is a common cellular mechanism underlying effects of different types of antidepressant treatments, and demonstrate a novel role for excitation/inhibition balance in bidirectional regulation of the state of neuronal maturation in the adult brain. Mice were decapitated after the 11 times of ECS (or Sham) or 4 weeks treatment of fluoxetine (or vehicle) at a dose of 22 mg/kg. The brains were sliced and the frequency facilitation of mossy fiber synapse was measured in each sample. The samples which exhibited low frequency facilitation were selected to be used as dematured DG (n = 3) and the dentate gyrus was dissected from each sample. Total RNA was extracted by using an RNeasy micro kit (Qiagen) and the samples of the same groups were put together. From each group, 100 ng of total RNA was amplified with 3M-bM-^@M-^YIVT Express kit (Affymetrix, Inc., Santa Clara, CA, USA). All samples were hybridized to the GeneChip mouse genome 430A 2.0 array (Affymetrix, Inc.), and the microarray suite 5.0 of the Affymetrix gene chip operating software was used for the analysis of the GeneChip data.
2014-04-01 | E-GEOD-54307 | biostudies-arrayexpress
Project description:Serial analysis of gene expression (SAGE) was used to get a global view of the gene profile in human hippocampus. A library were generated from control hippocampus, obtained by rapid autopsy. Keywords: hippocampus human inventory genes Control hippocampus (used to construct the SAGE control library) was obtained from a 48 years old man without history of seizures or other neurological diseases and no brain abnormalities at autopsy and histologically normal hippocampus. Autopsy was performed within 4 hours after death. Tissue was snap-frozen and stored at –80 0C until use. Total RNA was isolated from control hippocampus and hippocampal surgical specimens, using the Trizol method according to the manufacturer’s instructions (Invitrogen - Life Technologies, The Netherlands). Part of the anterior hippocampus of control (including sectors CA1- CA4 and dentate gyrus, DG) was used. Poly(A)+ RNA isolation, cDNA synthesis and all subsequent steps of the SAGE procedure were essentially performed as described (Velculescu et al., 1995) with minor modifications given previously (Michiels et al., 1999).
2005-12-29 | E-GEOD-3928 | biostudies-arrayexpress
Project description:Lysophosphatidic acid receptor 1 (LPA1) is a phospholipid which has been linked to adult hippocampal neurogenesis and learning deficits. Here we investigated whether LPA acts directly on the hippocampal stem cells and whether LPA1 could be a functional marker for their prospective isolation. Our results reveal that exogenous LPA increases precursor potential in vitro and net neurogenesis in vivo, an effect that is mediated by Akt activation. Using a mouse reporter line, immunohistochemistry and flow cytometry followed by in vitro cell culture, we show that, in contrast to the subventricular zone, neural precursor cells in the adult mouse dentate gyrus express LPA1-GFP. Fluorescence-activated cell sorting for LPA1-GFP in combination with Prominin-1 and epidermal growth factor receptor expression allowed the efficient isolation of a very pure population of hippocampal stem cells. Transcriptional analysis revealed a profile suggesting immune response and cytokine signaling as molecular regulators of adult hippocampal neural stem cells. RNA from cells sorted (FACS) from the dentate gyrus of adult LPA1-GFP (lysophosphatidic acid receptor) reporter mice. Sorting was based on the markers EGFR (Egfr), LPA1 (Lpar1) and Prominin1 (Prom1). From each of 4 replicates, 3 populations (stem cells, progenitor cells, niche cells) were sequenced.
2016-07-03 | E-GEOD-68270 | biostudies-arrayexpress
Project description:Analysis of the dentate gyrus of amygdala electrical stimulation model of temporal lobe epilepsy. Results provide insight into the molecular mechanism underlying epileptogenesis. This study was designed to estimate changes in miRNA expression levels after 7, 14, 30 and 90 days after electrical stimulation of amygdala as a model of temporal lobe epilepsy. The advantage of this study is time matched control (sham operated animals sacrificed at the same age as stimulated animals).
2013-08-14 | E-GEOD-49850 | biostudies-arrayexpress
Project description:Hippocampal sclerosis (HS) is the most common neuropathological finding of medically intractable cases of mesial temporal lobe epilepsy (MTLE), the most common form of partial epilepsy. Within the dentate gyrus, HS may be associated with granule cell dispersion and aberrant mossy fiber sprouting, and these pathological changes are accompanied by a range of molecular changes. In this study, we analyzed the gene expression profiles of dentate granule cells of MTLE patients with and without HS to show that next-generation sequencing methods can produce interpretable genomic data from RNA collected from small homogenous cell populations and to shed light on the transcriptional changes associated with HS. 12 samples of dentate granule cells from patients with mesial tempora lobe epilepsy, 5 with hippocampal sclerosis and 7 without hippocampal sclerosis. 10 samples had replicates.
2016-06-29 | E-GEOD-71058 | biostudies-arrayexpress