Hippocampal subfield transcriptomic profiles: Regional vulnerability to age and cognitive impairment
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE97608 | GEO | 2017/12/08
SECONDARY ACCESSION(S): PRJNA382422
REPOSITORIES: GEO
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Project description:The current study employed next generation RNA sequencing using two different platforms (Illumina and Ion Proton) to examine gene expression differences related to brain aging, cognitive decline, and hippocampus subregions (CA1, CA3, DG). Young and aged rats were trained on a spatial episodic memory task. The results describe regional differences in gene expression and point to regional differences in vulnerability to aging. Aging was associated with increased expression of immune response related genes, particularly in the dentate gyrus. For the memory task, impaired performance of aged animals was linked to the regulation of Ca2+ and synaptic function in region CA1. Finally, we provided a transcriptomic characterization of the three subregions regardless of age or cognitive status, highlighting and confirming a correspondence between cytoarchitectural boundaries and molecular profiling.
2017-12-08 | GSE101798 | GEO
Project description:Metabolic, mitochondrial and behavioral correlations with transcriptional profiles from the CA1 and DG hippocampal regions of young and aged rhesus macaque. Increasing evidence indicates that obesity correlates with impaired cognitive performance during normal aging and is a major risk factor for Alzheimer’s disease. However, little is known regarding how peripheral metabolic variables affect cellular pathways in brain regions important for memory. Brain inflammation, mitochondrial dysregulation, and altered transcriptional regulation have all been found to occur with aging, and recent microarray analyses in rodent models have linked these processes and others to age-related memory impairment. However, whether these brain changes are also associated with metabolic variables is not known. Aging monkeys exhibit several metabolic changes similar to those seen in humans. Here, we tested peripheral-brain relationships in six young (7.0 +/- 0.3 years) and six aged (23.5 +/- 0.7 years) female rhesus monkeys. Animal cognition was gauged with a variable delay task; blood constituents were assessed with a serum chemistry panel emphasizing markers of metabolic dysfunction; mitochondrial function was measured from the hippocampus of one hemisphere; and the CA1 and dentate gyrus regions of the other hippocampus were dissected out for gene expression microarray analysis. Aged animals showed reduced performance on the behavioral task, exhibited aspects of metabolic dysregulation including increased insulin, triglyceride, and chylomicron levels (consolidated into a peripheral metabolic index), and showed a significant age-related reduction in State III oxidation, a measure of mitochondrial function. Microarray analyses revealed hundreds of genes that correlated with the peripheral metabolic index. However, DAVID statistical pathway analyses showed that upregulated inflammatory genes in CA1 and downregulated transcriptional regulation genes in dentate gyrus and CA1 were particularly overrepresented among genes correlated with the peripheral index. Thus, the association of metabolic variables with specific neuropathological processes in different regions of the hippocampal formation may have implications for mechanisms through which peripheral metabolism alters the risk for Alzheimer’s disease. Keywords: Rhesus hippocampal aging
2010-04-15 | GSE11697 | GEO
Project description:Microarrays were used to assess the gene expression patterns in the CA1, CA3, and dentate gyrus of the rTg4510 mouse line at 4.5 months of age. This line harbors a repressible mutant human Tau transgene under the Camk2a promoter. Both mice with just the tet-Transactivator alone and no transgenes ('double negative') were used as comparison groups. Cellular layers of the CA1, CA3, and dentate gyrus (DG) from 5 or 6 mice per genotype at ages 4.5 months were laser capture dissected, RNA was isolated, and hybridization to Affymetrix microarrays performed.
2014-06-14 | E-GEOD-57528 | biostudies-arrayexpress
Project description:Microarrays were used to assess the gene expression patterns in the CA1, CA3, and dentate gyrus of the rTg4510 mouse line at 6.1 months of age. This line harbors a repressible mutant human Tau transgene under the Camk2a promoter. Both mice with just the tet-Transactivator alone and no transgenes ('double negative') were used as comparison groups. Cellular layers of the CA1, CA3, and dentate gyrus (DG) from 5 or 6 mice per genotype at age 6.1 months were laser capture dissected, RNA was isolated, and hybridization to Affymetrix microarrays performed.
2014-06-14 | E-GEOD-57583 | biostudies-arrayexpress
Project description:Identifying secreted mediators driving the cognitive benefits of exercise holds great promise for the treatment of cognitive decline in aging or Alzheimer’s disease (AD). Here, we show that irisin, the cleaved and circulating form of the exercise-induced membrane protein FNDC5, is sufficient to confer the exercise benefits on cognitive function. Genetic deletion of FNDC5/irisin (global F5KO mice) impairs cognitive function in exercise, aging, and AD. Diminished pattern separation in F5KOs can be rescued by delivering irisin directly into the dentate gyrus, suggesting that irisin is the active moiety. In F5KOs, adult-born neurons in the dentate gyrus are morphologically, transcriptionally, and functionally abnormal. Importantly, elevation of circulating irisin levels by peripheral administration, resulting in enrichment of central irisin, was sufficient to improve both the cognitive deficit and neuropathology in AD mouse models. Irisin is a crucial regulator of cognitive benefits of exercise and potential therapeutic for treating cognitive disorders including AD.
2021-08-11 | GSE179078 | GEO
Project description:Identifying secreted mediators driving the cognitive benefits of exercise holds great promise for the treatment of cognitive decline in aging or Alzheimer’s disease (AD). Here, we show that irisin, the cleaved and circulating form of the exercise-induced membrane protein FNDC5, is sufficient to confer the exercise benefits on cognitive function. Genetic deletion of FNDC5/irisin (global F5KO mice) impairs cognitive function in exercise, aging, and AD. Diminished pattern separation in F5KOs can be rescued by delivering irisin directly into the dentate gyrus, suggesting that irisin is the active moiety. In F5KOs, adult-born neurons in the dentate gyrus are morphologically, transcriptionally, and functionally abnormal. Importantly, elevation of circulating irisin levels by peripheral administration, resulting in enrichment of central irisin, was sufficient to improve both the cognitive deficit and neuropathology in AD mouse models. Irisin is a crucial regulator of cognitive benefits of exercise and potential therapeutic for treating cognitive disorders including AD.
2021-08-11 | GSE174211 | GEO
Project description:Identifying secreted mediators driving the cognitive benefits of exercise holds great promise for the treatment of cognitive decline in aging or Alzheimer’s disease (AD). Here, we show that irisin, the cleaved and circulating form of the exercise-induced membrane protein FNDC5, is sufficient to confer the exercise benefits on cognitive function. Genetic deletion of FNDC5/irisin (global F5KO mice) impairs cognitive function in exercise, aging, and AD. Diminished pattern separation in F5KOs can be rescued by delivering irisin directly into the dentate gyrus, suggesting that irisin is the active moiety. In F5KOs, adult-born neurons in the dentate gyrus are morphologically, transcriptionally, and functionally abnormal. Importantly, elevation of circulating irisin levels by peripheral administration, resulting in enrichment of central irisin, was sufficient to improve both the cognitive deficit and neuropathology in AD mouse models. Irisin is a crucial regulator of cognitive benefits of exercise and potential therapeutic for treating cognitive disorders including AD.
2021-08-11 | GSE174210 | GEO
Project description:Gene expression profiling in differential cognitive outcomes in aging: Dentate Gyrus
| PRJNA114345 | ENA
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:Previous studies of age-related transcriptional changes indicate that cognitive impairments are associated with differentially expressed genes DEGs linked to defined neural systems; however, studies that examine multiple regions of the hippocampus fail to find major links between behavior and transcription in the dentate gyrus DG. The DG is implicated in pattern separation PS and exhibits multiple age-related changes that may affect PS performance. We hypothesize that an age-related decline in PS performance is associated with distinct changes in transcriptional profile, most strongly within the DG compared to other hippocampal subregions. We used a water maze beacon discrimination task to characterize PS in young 5 mo and middle-age 12 mo male F344 rats, followed by a spatial reference memory test. Middle-age rats showed consistent deficits in discriminating two identical beacons compared to young. Reference memory was not different between these two age groups. Interestingly, with increasing spatial overlap between the cues, older animals appeared to compensate for impaired PS performance though greater reliance on spatial reference memory. mRNA sequencing of hippocampal subregions DG, CA1, and CA3 indicated that the DG of middle-age rats expressed more genes correlated with PS performance. In contrast, reliance on a spatial reference memory was associated with differential expression of genes in regions CA1 and CA3. These results indicate that the beacon task is sensitive to PS impairment as early as middle-age, and distinct gene profiles are observed in neural circuits that underlie different strategies used to solve the task.
2020-05-22 | GSE140420 | GEO