Transcription profiling of mouse hippocampus to identify gene expression changes during age-related cognitive decline
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Traci Pawlowski
PROVIDER: E-GEOD-13799 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Comparison of hippocampal gene expression between normal young animals and older animals with good spatial memory and older animals with poor spatial memory
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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.
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Project description:Mice deficient in the glucocorticoid-regenerating enzyme 11β-HSD1 resist age-related spatial memory impairment. To investigate the mechanisms/pathways involved, we used microarrays to identify differentially expressed hippocampal genes that associate with cognitive ageing and 11β-HSD1. Aged wild-type mice were separated into memory-impaired and unimpaired relative to young controls according to their performance in the Y-maze. All individual aged 11β-HSD1-deficient mice showed intact spatial memory. The majority of differentially expressed hippocampal genes were increased with ageing (e.g. immune/inflammatory response genes) with no genotype differences. However, the neuronal-specific transcription factor, Npas4 and immediate early gene, Arc were reduced (relative to young) in the hippocampus of memory-impaired but not unimpaired aged wild-type or aged 11β-HSD1-deficient mice. Quantitative RT-PCR and in situ hybridization confirmed reduced Npas4 and Arc mRNA expression in memory-impaired aged wild-type mice. These findings suggest that 11β-HSD1 may contribute to the decline in Npas4 and Arc mRNA levels associated with memory impairment during ageing, and that decreased activity of synaptic plasticity pathways involving Npas4 and Arc may, in part, underlie the memory deficits seen in cognitively-impaired aged wild-type mice. 20 samples, 5 groups of 4 biological replicates each. Young, Wild Type animals are overall controls
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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.
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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.
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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.
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Project description:A theoretical framework for the function of the medial temporal lobe system in memory defines differential contributions of the hippocampal subregions with regard to pattern recognition retrieval processes and encoding of new information. To investigate molecular programs of relevance, we designed a spatial learning protocol to engage a pattern separation function to encode new information. After background training, two groups of animals experienced the same new training in a novel environment, however only one group was provided spatial information and demonstrated spatial memory in a retention test. Global transcriptional analysis of the microdissected subregions of the hippocampus exposed a CA3 pattern that was sufficient to clearly segregate spatial learning animals from control. Individual gene and functional group analysis anchored these results to previous work in neural plasticity. From a multitude of expression changes, increases in camk2a, rasgrp1 and nlgn1 were confirmed by in situ hybridization. Furthermore, siRNA inhibition of nlgn1 within the CA3 subregion impaired spatial memory performance, pointing to mechanisms of synaptic remodeling as a basis for rapid encoding of new information in long-term memory. Experiment Overall Design: RNA samples from animals subjected to a spatial learning paradigm were compared to controls using Affymetirx RAE230a chips. An N of 6 was used in each of the two experimental conditions.
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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. Keywords: behavior comparison, age comparison
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