Rattus norvegicus
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ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-34424
PROVIDER: PRJNA149553 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The Influence of Sleep Deprivation on Hippocampal CA1 Gene Expression: Relation to Stress and Aging
2015-07-27 | E-GEOD-34424 | ExpressionAtlas
Project description:Sleep deprivation (SD) in young adults is associated with metabolic, stress and cognitive responses that are also characteristic of brain aging. Given that sleep architecture changes with age, including increased fragmentation and decreased slow wave activity, it seems reasonable to investigate potential molecular relationships between SD and aging in brain tissue. Here, we tested the hypothesis that young rats exposed to 24 or 72 hour SD would respond with stress and aging-like shifts in brain hippocampal CA1 gene expression. SD animals showed blood corticosterone and weight changes consistent with a stress response. Microarray results, validated by Western blot and comparison to prior SD studies, pointed to disruptions in neurotransmission, sleep pressure signaling, and macromolecular synthesis. In a separate experiment, animals exposed to 24 or 72 hour novel environment stress recapitulated nearly one third of the SD transcriptional profile, particularly upregulated apoptotic and immune signaling pathways. Compared to aging (based on three previously published independent hippocampal aging studies), SD transcriptional profiles agreed for neurogenesis and energy pathways. However, immune signaling, glial activity, macromolecular synthesis and neuronal function all showed an SD profile that was, at least in part, opposed by aging. We conclude that while stress and SD have discrete molecular signatures, they do show a subset of highly similar changes. However, the same could not be said of aging and SD, where a similar subset of genes is changed, but in partially divergent directions. Finally, this work identifies presynaptic vesicular release and intercellular adhesion molecular signatures as novel targets for future SD-countering therapeutics. Subjects: Male Fischer 344 rats (3-5 months old, Harlan, Indianapolis): 37 in cohort 1 and 32 in cohort 2. Subjects were assigned to one of 5 treatment groups: Home Cage-HC n =17; 24 hour sleep deprivation- 24SD n = 16; 72 hour sleep deprivation- 72SD n = 20; 24 hour novel environment stress- 24NES n = 10; 72 hour novel environment stress- 72NES n = 6. Cohorts 1 and 2 were combined for microarray analyses. Sleep Deprivation: The multiple platform modification (Coenen and van Luijtelaar, 1985) of the classic 'flower pot' (Mendelson et al., 1974) technique in which animals are placed on an elevated platform over water was used. Pairs of SD animals (cage mates) were sleep deprived for 24 or 72 hours. Novel Environment Stress (NES): NES animals were exposed to a novel environment, but were not constrained from sleeping. These NES animals paralleled the sleep deprivation exposure duration (24 hour- n = 10, and 72 hour- n = 6). Tissue Isolation: On the day that animals were removed from the SD chambers, they were anesthetized with CO2 gas and decapitated. Brains were removed and immediately placed in oxygenated artificial cerebrospinal fluid (aCSF) containing (in mM) 114NaCl, 2.5 KCl, 2MgCl2, 30 NaHCO3, 10 Glucose and 2.2CaCl2. Hippocampi were dissected as described previously (Blalock et al., 2003; Kadish et al., 2009). Briefly, dissected hippocampi were immersed in 0C oxygenated aCSF and placed on a chilled glass petri dish. The CA1 region was dissected along the long axis of the hippocampus. CA1 tissue was flash frozen and stored at -80C until further use. Microarray Protocol: GCOS quality control measures of background signal (74.9 ± 2.1 cohort 1; 59.8 ± 2.3 cohort 2) and RawQ (2.3 ± 0.1 cohort 1; 1.9 ± 0.1 cohort 2), as well as a chip x chip correlation matrix of signal intensity data pointed to a global decrease in background signal intensity in Cohort 2. To control for this, each gene expression values for HC, 24SD and 72SD was standardized separately within cohort 1 and cohort 2, and then the two cohorts were combined. This retained the variability of each cohort, but removed the 'cohort effect' from the data. Pre-statistical filtering retained 'A' grade probe sets that were uniquely annotated (Affymetrix, June 2011) with gene symbols and had at least 6 presence calls across all 71 chips. This criterion was selected based on factorial analysis demonstrating < 5% probability of 6 or more chips being rated present for a given probe set by chance (Blalock, unpublished observations).
2012-07-16 | E-GEOD-34424 | biostudies-arrayexpress
Project description:Transcriptional profiles of rodent hippocampal CA1 tissue during aging and cognitive decline
| PRJNA104011 | ENA
Project description:Sleep deprivation (SD) in young adults is associated with metabolic, stress and cognitive responses that are also characteristic of brain aging. Given that sleep architecture changes with age, including increased fragmentation and decreased slow wave activity, it seems reasonable to investigate potential molecular relationships between SD and aging in brain tissue. Here, we tested the hypothesis that young rats exposed to 24 or 72 hour SD would respond with stress and aging-like shifts in brain hippocampal CA1 gene expression. SD animals showed blood corticosterone and weight changes consistent with a stress response. Microarray results, validated by Western blot and comparison to prior SD studies, pointed to disruptions in neurotransmission, sleep pressure signaling, and macromolecular synthesis. In a separate experiment, animals exposed to 24 or 72 hour novel environment stress recapitulated nearly one third of the SD transcriptional profile, particularly upregulated apoptotic and immune signaling pathways. Compared to aging (based on three previously published independent hippocampal aging studies), SD transcriptional profiles agreed for neurogenesis and energy pathways. However, immune signaling, glial activity, macromolecular synthesis and neuronal function all showed an SD profile that was, at least in part, opposed by aging. We conclude that while stress and SD have discrete molecular signatures, they do show a subset of highly similar changes. However, the same could not be said of aging and SD, where a similar subset of genes is changed, but in partially divergent directions. Finally, this work identifies presynaptic vesicular release and intercellular adhesion molecular signatures as novel targets for future SD-countering therapeutics.
2012-07-17 | GSE34424 | GEO
Project description:Time-dependent response of hippocampal CA1 and CA3 to oxidative stress
| PRJNA99049 | ENA
Project description:Calorie restriction (CR) enhances longevity and mitigates aging phenotypes in numerous species. Physiological responses to CR are cell-type specific and variable throughout the lifespan; however, the mosaic of molecular changes responsible CR benefits remain unclear, particularly in brain regions susceptible to deterioration throughout aging. Thus, we examined the influence of long-term CR on the CA1 hippocampal region, a key learning and memory brain area that is vulnerable to age-related pathologies, such as Alzheimerâs disease (AD). Through mRNA sequencing and NanoString nCounter analysis, we demonstrate that one year of CR feeding suppresses an age-dependent signature of 882 genes functionally associated with synaptic transmission-related pathways, including calcium signaling, long-term potentiation (LTP), and Creb signaling in wild-type mice. By comparing the influence of CR on hippocampal CA1 region transcriptional profiles at younger- (5 months) and older-adult (15 months) timepoints, we identify conserved upregulation of proteome quality control and calcium buffering genes, including heat shock 70 kDa proteins 1b and 5 (Hspa1b and Hspa5), protein disulfide isomerase family A members 4 and 6 (Pdia4 and Pdia6), and calreticulin (Calr). Expression levels of putative neuroprotective factors, klotho (Kl) and transthyretin (Ttr), are also elevated by CR throughout adulthood, although the global CR-specific expression profiles at young and older timepoints are highly divergent. At a previously unachieved resolution, our results demonstrate conserved activation of neuroprotective gene signatures and broad CR-suppression of age-dependent hippocampal CA1 region expression changes, indicating that CR functionally maintains a more youthful transcriptional state within hippocampal CA1 throughout aging. Hippocampal CA1 region mRNA profiles of younger- (5 months) and older-adult (15 months) mice on calorie-restricted (CR) and normal (AD) diets were generated by deep sequencing using Illumina HiSeq 2500.
2015-07-14 | E-GEOD-69952 | biostudies-arrayexpress
Project description:We used microarrays to detail the global programme of gene expression underlying the effect of sleep deprivation in the mouse hippocampus and identified distinct classes of regulated genes during this process. Hippocampal tissue was taken from sleep deprived mice and time-matched non-sleep-deprived control animals that were left undisturbed in their home cages during the sleep deprivation period for a total of 8 and 9 replicates per group. RNA was isolated and cDNA was synthesized from hippocampal tissue, and the sample from each animal was hybridized to a separate Affymetrix Mouse 430_2 microarray
2012-09-06 | E-GEOD-33302 | biostudies-arrayexpress
Project description:Post-learning sleep plays an important role in hippocampal memory processing, including contextual fear memory (CFM) consolidation. Here, we used targeted recombination in activated populations (TRAP) to label context-encoding engram neurons in the hippocampal dentate gyrus (DG) and assessed reactivation of these neurons during post-learning sleep. We find that post-learning sleep deprivation (SD), which impairs CFM consolidation, selectively disrupts reactivation in inferior blade DG engram neurons. This change was linked to more general suppression of neuronal activity markers in the inferior, but not superior, DG blade by SD. To further characterize how learning and subsequent sleep or SD affect these (and other) hippocampal subregions, we used subregion-specific spatial profiling of transcripts and proteins. We found that transcriptomic responses to sleep loss differed greatly between hippocampal regions CA1, CA3, and DG inferior blade, superior blade, and hilus. Critically, learning-driven transcriptomic changes, measured 6 h following contextual fear learning, were limited to the two DG blades, differed dramatically between the blades, and were absent from all other regions. Similarly, protein abundance in these hippocampal subregions were differentially impacted by sleep vs. SD and by prior learning, with the majority of alterations to protein expression restricted to DG. Together, these data suggest that the DG plays an essential role in the consolidation of hippocampal memories, and that the effects of sleep and sleep loss on the brain are highly subregion-specific, even within the DG itself.
2024-03-01 | GSE229080 | GEO
Project description:Post-learning sleep plays an important role in hippocampal memory processing, including contextual fear memory (CFM) consolidation. Here, we used targeted recombination in activated populations (TRAP) to label context-encoding engram neurons in the hippocampal dentate gyrus (DG) and assessed reactivation of these neurons during post-learning sleep. We find that post-learning sleep deprivation (SD), which impairs CFM consolidation, selectively disrupts reactivation in inferior blade DG engram neurons. This change was linked to more general suppression of neuronal activity markers in the inferior, but not superior, DG blade by SD. To further characterize how learning and subsequent sleep or SD affect these (and other) hippocampal subregions, we used subregion-specific spatial profiling of transcripts and proteins. We found that transcriptomic responses to sleep loss differed greatly between hippocampal regions CA1, CA3, and DG inferior blade, superior blade, and hilus. Critically, learning-driven transcriptomic changes, measured 6 h following contextual fear learning, were limited to the two DG blades, differed dramatically between the blades, and were absent from all other regions. Similarly, protein abundance in these hippocampal subregions were differentially impacted by sleep vs. SD and by prior learning, with the majority of alterations to protein expression restricted to DG. Together, these data suggest that the DG plays an essential role in the consolidation of hippocampal memories, and that the effects of sleep and sleep loss on the brain are highly subregion-specific, even within the DG itself.
2024-03-01 | GSE229081 | GEO