Molecular profiles of cognitive aging
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE46193 | GEO | 2013/04/19
SECONDARY ACCESSION(S): PRJNA198006
REPOSITORIES: GEO
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Project description:Gene expression was measured from the dentate gyrus and entorhinal cortex harvested from human postmortem samples. We harvested the dentate gyrus DG from healthy human brains ranging from 33 to 88 years of age. Additionally, from each brain we harvested the entorhinal cortex (EC) as a within-brain control. Using Affymetrix microarray chips we generated gene-expression profiles of each individual tissue samples. DG expression levels were first normalized against the EC, and the normalized DG transcripts were then correlated against age.
2013-04-19 | E-GEOD-46193 | biostudies-arrayexpress
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Project description:Sanfilippo syndrome type B (MPS III B) is an autosomal recessive, neurodegenerative disease of children, characterized by profound mental retardation and dementia. The primary cause is mutation in the NAGLU gene, resulting in deficiency of N-acetylglucosaminidase and lysosomal accumulation of heparan sulfate. In the mouse model of MPS III B, neurons and microglia display the characteristic vacuolation of lysosomal storage of undegraded substrate, but neurons in the medial entorhinal cortex (MEC) display accumulation of several additional substances. We used whole genome microarray analysis to examine differential gene expression in MEC neurons isolated by laser capture microdissection from Naglu -/- and Naglu +/- mice. Neurons from the lateral entorhinal cortex (LEC) were used as tissue controls. The highest increase in gene expression (6- to 7-fold between mutant and control) in MEC and LEC neurons was that of Lyzs, which encodes lysozyme, but accumulation of lysozyme protein was seen in MEC neurons only. Because of a report that lysozyme induced the formation of hyperphosphorylated tau (P-tau) in cultured neurons, we searched for P-tau by immunohistochemistry. P-tau was found in MEC of Naglu -/- mice, in the same neurons as lysozyme. In older mutant mice, it was also seen in the dentate gyrus, an area important for memory. Electron microscopy of dentate gyrus neurons showed cytoplasmic inclusions of paired helical filaments - P-tau aggregates characteristic of tauopathies, a group of age-related dementias that includes Alzheimer disease. Our findings indicate that the Sanfilippo syndrome type B should also be considered a tauopathy. Two-condition experiment, Naglu-/- (affected) vs. Naglu+/- (unaffected control) of neurons from two adjacent brain regions: medial entorhinal cortex (MEC) and lateral entorhinal cortex (LEC). Biological replicates: 3 MEC Naglu-/-, 3 MEC Naglu+/-, 3 LEC Naglu-/- and 3 LEC Naglu+/-. Comparisons were made between 3 pairs of mutant and control female littermates for MEC and LEC neurons with dye switch duplicates, for a total of 12 microarrays.
2009-04-22 | E-GEOD-15758 | biostudies-arrayexpress
Project description:Gene expression profiles were assessed in the hippocampus (HC), entorhinal cortex (EC), superior frontal gyrus (SG), and postcentral gyrus (PCG) across the lifespan of 63 cognitively intact individuals from 20-99 years old. New perspectives on the global gene changes that are associated with brain aging emerged, revealing two overarching concepts. First, different regions of the forebrain exhibited substantially different gene profile changes with age. For example, comparing equally powered groups, 5,029 probe sets were significantly altered with age (20-59 vs. 60-99) in the superior frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change occurred in the 6th-7th decades across cortical regions, suggesting that this period is a critical transition point in brain aging, particularly in males. Second, clear gender differences in brain aging were evident across the lifespan, suggesting that the brain undergoes sexually dimorphic changes in gene expression not only in development but also in later life. Globally across all brain regions, males showed more gene change than females. Further, Gene Ontology analysis revealed that different categories of genes were predominantly affected in males vs. females. Notably, the male brain was characterized by global decreased catabolic and anabolic capacity with aging, with downregulated genes heavily enriched in energy production and protein synthesis/transport categories. Increased immune activation was a prominent feature of aging in both sexes, with more widespread activation in the female brain. These data open new opportunities to explore age-dependent changes in gene expression that set the balance between neurodegeneration and compensatory mechanisms in the brain, and suggest that this balance is set differently in males and females, an intriguing and novel idea. HgU133plus2.0 microarray chips were used to profile gene expression in 4 brain regions of cognitively intact humans, across the adult lifespan (ages 20-99). Experiment Overall Design: Postmortem brain tissue was collected from ADRC brain banks. Cases were preferentially selected where 3 or more brain regions were available.
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Project description:Layer II stellate neurons (entorhinal cortex) and layer III cortical neurons (hippocampus CA1, middle temporal gyrus, posterior cingulate, superior frontal gyrus, primary visual cortex) were gene expression profiled. Brain regions are from non-demented individuals with intermediate Alzheimer's disease neuropathologies Keywords: neuronal gene expression profiling
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Project description:The dentate gyrus of the hippocampus is a brain region involved in learning, memory formation, and spatial coding. We performed single-cell RNA-sequencing of the dentate gyrus of young and old mice to identify the age-induced changes.
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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.
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