Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA208130 | ENA |
REPOSITORIES: ENA
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Project description:Aging is often associated with cognitive decline, but many elderly individuals maintain a high level of function throughout life. Here we studied outbred rats, which also exhibit individual differences across a spectrum of outcomes that includes both preserved and impaired spatial memory. Previous work in this model identified the CA3 subfield of the hippocampus as a region critically affected by age and integral to differing cognitive outcomes. Earlier microarray profiling revealed distinct gene expression profiles in the CA3 region, under basal conditions, for aged rats with intact memory and those with impairment. Because prominent age-related deficits within the CA3 occur during neural encoding of new information, here we used microarray analysis to gain a broad perspective of the aged CA3 transcriptome under activated conditions. Behaviorally induced CA3 expression profiles differentiated aged rats with intact memory from those with impaired memory. In the activated profile, we observed substantial numbers of genes (greater than 1000) exhibiting increased expression in aged unimpaired rats relative to aged impaired, including many involved in synaptic plasticity and memory mechanisms. This unimpaired aged profile also overlapped significantly with a learning induced gene profile previously acquired in young adults. Alongside the increased transcripts common to both young learning and aged rats with preserved memory, many transcripts behaviorally-activated in the current study had previously been identified as repressed in the aged unimpaired phenotype in basal expression. A further distinct feature of the activated profile of aged rats with intact memory is the increased expression of an ensemble of genes involved in inhibitory synapse function, which could control the phenotype of neural hyperexcitability found in the CA3 region of aged impaired rats. These data support the conclusion that aged subjects with preserved memory recruit adaptive mechanisms to retain tight control over excitability under both basal and activated conditions. RNA profiles from cognitively unimpaired and impaired aged rats were compared under 2 conditions: spatial learning task and a non-spatial learning task.
2013-12-16 | E-GEOD-47867 | biostudies-arrayexpress
Project description:Aging is often associated with cognitive decline, but many elderly individuals maintain a high level of function throughout life. Here we studied outbred rats, which also exhibit individual differences across a spectrum of outcomes that includes both preserved and impaired spatial memory. Previous work in this model identified the CA3 subfield of the hippocampus as a region critically affected by age and integral to differing cognitive outcomes. Earlier microarray profiling revealed distinct gene expression profiles in the CA3 region, under basal conditions, for aged rats with intact memory and those with impairment. Because prominent age-related deficits within the CA3 occur during neural encoding of new information, here we used microarray analysis to gain a broad perspective of the aged CA3 transcriptome under activated conditions. Behaviorally induced CA3 expression profiles differentiated aged rats with intact memory from those with impaired memory. In the activated profile, we observed substantial numbers of genes (greater than 1000) exhibiting increased expression in aged unimpaired rats relative to aged impaired, including many involved in synaptic plasticity and memory mechanisms. This unimpaired aged profile also overlapped significantly with a learning induced gene profile previously acquired in young adults. Alongside the increased transcripts common to both young learning and aged rats with preserved memory, many transcripts behaviorally-activated in the current study had previously been identified as repressed in the aged unimpaired phenotype in basal expression. A further distinct feature of the activated profile of aged rats with intact memory is the increased expression of an ensemble of genes involved in inhibitory synapse function, which could control the phenotype of neural hyperexcitability found in the CA3 region of aged impaired rats. These data support the conclusion that aged subjects with preserved memory recruit adaptive mechanisms to retain tight control over excitability under both basal and activated conditions.
2013-12-16 | GSE47867 | GEO
Project description:The aim of this study was to investigate whether the differences in memory decline associated with aging are a result of differences in gene expression. We first categorized age-unimpaired and age-impaired rats based on their performance in the Morris water maze, when compared to young rats. Then we isolated messenger RNA from the dentate gyrus of the hippocampus of each animal to interrogate Affymetrix RAE 230A rat genome microarrays. Supervised statistical analysis of the different groups of aged animals recognized 85 genes (p<0.005) that were significantly different in the dentate gyrus of aged rats that had learned the Morris water maze (MWM) paradigm when compared to learning impaired and a number of controls for stress, exercise and non-spatial learning. In addition, statistical analysis of the microarray data that included young and aged rats identified 1129 genes (p<0.005) that were differentially expressed between aged and young rats independent of behavior, but due to aging alone. Experiment Overall Design: a total of 80 samples were analyzed including aged and young rats for aged versus young comparisons. One chip was interrogated per animal. Supervised analysis of aged rat data (aged unimpaired (HID U) versus controls : HID I, VIS, YOKE, SIT includes 39 samples (intermediate learners were not included in the analysis). Controls include cage controls, yoke controls (no platform), visible platform controls.
2008-06-13 | E-GEOD-4821 | biostudies-arrayexpress
Project description:The aim of this study was to investigate whether the differences in memory decline associated with aging are a result of differences in gene expression. We first categorized age-unimpaired and age-impaired rats based on their performance in the Morris Water Maze and then isolated messenger RNA from the CA1 hippocampal region of each animal to interrogate Affymetrix microarrays. Microarray analysis (p<0.005) identified a set of 50 genes that were transcribed differently in age-unimpaired animals that had successfully learned a spatial task compared to aged learning-impaired animals and a variety of groups designed to control for all non-learning aspects of exposure to the water maze paradigm. Experiment Overall Design: a total of 79 samples were analyzed including aged and young rats. One chip was interrogated per animal. Analysis of aged rat data includes 44 samples. Controls include cage controls, yoked controls (no platform), visible platform controls.
2007-11-06 | E-GEOD-3531 | biostudies-arrayexpress
Project description:Aging is associated with a decline in hippocampal mediated learning and memory, a process which can be ameliorated by dietary (caloric) restriction. We used Affymetrix gene expression analysis to monitor changes in three regions of the hippocampus (CA1, CA3, DG) of middle aged (18 months) and old (28 month) rats that were exposed to dietary restriction. Old rats were determined to be good performers (GP) or poor performers (PP) in behavioural tests to assess their hippocampal function. We used Affymetrix gene expression analysis to monitor changes in three regions of the hippocampus (CA1, CA3, DG) of middle aged (18 months) and old (28 month) rats that were exposed to dietary restriction.
2010-06-08 | E-GEOD-21681 | biostudies-arrayexpress
Project description:The aim of this study was to investigate whether the differences in memory decline associated with aging are a result of differences in gene expression. We first categorized age-unimpaired and age-impaired rats based on their performance in the Morris water maze, when compared to young rats. Then we isolated messenger RNA from the dentate gyrus of the hippocampus of each animal to interrogate Affymetrix RAE 230A rat genome microarrays. Supervised statistical analysis of the different groups of aged animals recognized 85 genes (p<0.005) that were significantly different in the dentate gyrus of aged rats that had learned the Morris water maze (MWM) paradigm when compared to learning impaired and a number of controls for stress, exercise and non-spatial learning. In addition, statistical analysis of the microarray data that included young and aged rats identified 1129 genes (p<0.005) that were differentially expressed between aged and young rats independent of behavior, but due to aging alone. Keywords: behavior comparison, age comparison
2007-07-31 | GSE4821 | GEO
Project description:Enzastaurin is a Protein Kinase C-β selective inhibitor that was developed to treat cancers. Protein Kinase C-β is an important enzyme for a variety of neuronal functions; in particular, previous rodent studies have reported deficits in spatial and fear-conditioned learning and memory with lower levels of Protein Kinase C-β. Due to Enzastaurin’s mechanism of action, the present study investigated the consequences of Enzastaurin exposure on learning and memory in 12-month-old Fischer-344 male rats. Rats were treated daily with subcutaneous injections of either vehicle or Enzastaurin, and behaviorally tested using the spatial reference memory Morris Water Maze. Rats treated with Enzastaurin exhibited decreased overnight retention and poorer performance on the latter testing day, indicating a mild, but significant, memory impairment. There were no differences during the probe trial indicating that all animals were able to spatially localize the platform to the proper quadrant by the end of testing. RNA isolated from the hippocampus was analyzed using Next Generation Sequencing (Illumina). No statistically significant transcriptional differences were noted. Our findings suggest that acute Enzastaurin treatment can impair hippocampal-based learning and memory performance, with no effects on transcription in the hippocampus. We propose that care should be taken in future clinical trials that utilize Protein Kinase C-ß inhibitors, to monitor for possible cognitive effects, future research should examine if these effects are fully reversible.
2018-04-20 | GSE113327 | GEO
Project description:Functional alterations in medial temporal lobe structures, particularly the hippocampus, are central to age-related deficits in episodic memory. Research in aging laboratory animals has characterized physiological and cellular alterations in the hippocampus that occur in association with the presence and severity of such cognitive impairment. The current study compares alterations across hippocampal subregions by gene expression profiling in a rat model that closely mirrors individual differences in neurocognitive features of aging humans across a spectrum of outcomes, including both impaired memory and preserved function. Using mRNA profiling of the CA1, CA3 and dentate gyrus subregions, we have distinguished between gene groups and pathways related to chronological age and those specifically associated with impaired or preserved cognitive ability in aged rats. We confirmed earlier reported changes in gene groups related to inflammation and oxidative stress in multiple subregions and found these to be more associated with chronological age than cognitive function per se. The CA3 profile was best able to segregate aged impaired, aged unimpaired and young subject groups from each other. Characterization of gene changes that distinguished preserved from impaired function among the aged animals found altered expression of synaptic plasticity and neurodegenerative disease-related genes. Together these gene changes suggest recruitment of adaptive mechanisms that mediate synaptic plasticity to maintain function and structural integrity in aged unimpaired rats that does not occur in aged impaired animals.
2009-11-01 | GSE14725 | GEO
Project description:Functional alterations in medial temporal lobe structures, particularly the hippocampus, are central to age-related deficits in episodic memory. Research in aging laboratory animals has characterized physiological and cellular alterations in the hippocampus that occur in association with the presence and severity of such cognitive impairment. The current study compares alterations across hippocampal subregions by gene expression profiling in a rat model that closely mirrors individual differences in neurocognitive features of aging humans across a spectrum of outcomes, including both impaired memory and preserved function. Using mRNA profiling of the CA1, CA3 and dentate gyrus subregions, we have distinguished between gene groups and pathways related to chronological age and those specifically associated with impaired or preserved cognitive ability in aged rats. We confirmed earlier reported changes in gene groups related to inflammation and oxidative stress in multiple subregions and found these to be more associated with chronological age than cognitive function per se. The CA3 profile was best able to segregate aged impaired, aged unimpaired and young subject groups from each other. Characterization of gene changes that distinguished preserved from impaired function among the aged animals found altered expression of synaptic plasticity and neurodegenerative disease-related genes. Together these gene changes suggest recruitment of adaptive mechanisms that mediate synaptic plasticity to maintain function and structural integrity in aged unimpaired rats that does not occur in aged impaired animals.
2009-11-01 | GSE14724 | GEO
Project description:Functional alterations in medial temporal lobe structures, particularly the hippocampus, are central to age-related deficits in episodic memory. Research in aging laboratory animals has characterized physiological and cellular alterations in the hippocampus that occur in association with the presence and severity of such cognitive impairment. The current study compares alterations across hippocampal subregions by gene expression profiling in a rat model that closely mirrors individual differences in neurocognitive features of aging humans across a spectrum of outcomes, including both impaired memory and preserved function. Using mRNA profiling of the CA1, CA3 and dentate gyrus subregions, we have distinguished between gene groups and pathways related to chronological age and those specifically associated with impaired or preserved cognitive ability in aged rats. We confirmed earlier reported changes in gene groups related to inflammation and oxidative stress in multiple subregions and found these to be more associated with chronological age than cognitive function per se. The CA3 profile was best able to segregate aged impaired, aged unimpaired and young subject groups from each other. Characterization of gene changes that distinguished preserved from impaired function among the aged animals found altered expression of synaptic plasticity and neurodegenerative disease-related genes. Together these gene changes suggest recruitment of adaptive mechanisms that mediate synaptic plasticity to maintain function and structural integrity in aged unimpaired rats that does not occur in aged impaired animals.
2009-11-01 | GSE14723 | GEO