Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of rat hippocampus from young and aged rats with age-related spatial learning impairments

ABSTRACT: 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.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Corinna Burger

PROVIDER: E-GEOD-3531 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Changes in transcription within the CA1 field of the hippocampus are associated with age-related spatial learning impairments.

Burger Corinna C López M Cecilia MC Feller Joyce A JA Baker Henry V HV Muzyczka Nicholas N Mandel Ronald J RJ

Neurobiology of learning and memory 20060710 1

Aged rats display a broad range of behavioral performance in spatial learning. The aim of this study was to identify candidate genes that are associated with learning and memory impairments. We first categorized aged-superior learners and age learning-impaired rats based on their performance in the Morris water maze (MWM) and then isolated messenger RNA from the CA1 hippocampal region of each animal to interrogate Affymetrix microarrays. Microarray analysis identified a set of 50 genes that was ...[more]

PMID: 16829144

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Project description:Although immediate early genes (IEGs) such as Bdnf, Arc and Egr1, have been implicated in plasticity, the larger pathways related to memory and memory disorders are not well understood. Here, we combined statistical Affymetrix microarray and behavioral analyses to identify key genes and pathways associated with aging-related cognitive impairment. Aged rats were separated into cognitively unimpaired (AU) or impaired (AI) groups, based on their Morris water maze performance relative to young-adult (Y) animals. Hippocampal gene expression was assessed in Y, AU and AI on the fifth (last) day of maze training or 21 days posttraining, and in non-trained aged and young animals (eight groups, overall n = 78, one chip/animal). ANOVA, linear contrasts, and overrepresentation analyses identified genes and pathways that differed from Y generally with aging (in both AU and AI) or selectively with cognitive status (only in AI or AU). Plasticity pathways, including insulin/cAMP/IEG signaling, and glycogenolytic and lipogenic pathways, were selectively downregulated (5 days) in AI, whereas Notch2 (regulating oligodendrocyte differentiation) and myelination pathways were upregulated (particularly at 21 days). Downregulation with general aging occurred in signal transduction and axonal growth/transport pathways, whereas upegulation occurred in immune/inflammatory, lipid metabolism/transport (e.g., Lxr-Srebf1), and lysosomal pathways. In AU, receptor/signal transduction genes were selectively upregulated, suggesting possible compensatory mechanisms. Immunohistochemistry confirmed and extended results to the protein level. Thus, this study identified novel cognition-linked processes, suggesting a new model in which energy-intensive, plasticity/lipogenic processes and energy-generating pathways necessary for learning are coordinately downregulated during training, while myelinogenic programs that impair cognition are concurrently activated. Experiment Overall Design: Aged rats were separated into cognitively unimpaired (AU) or impaired (AI) groups, based on their Morris water maze performance relative to young-adult (Y) animals (NT, 5D, and 21D, N=10/group). Hippocampal gene expression was assessed in Y, AU and AI on the fifth (last) day of maze training or 21 days posttraining, and in non-trained aged and young animals (eight groups, overall n = 78, one chip/animal)

Project description:The aim of this study was to characterize the basal expression of OC, MOD and SV of newborn rats (3-5 day old) and its changes by shortâterm cultivation (24 hrs) and mild hypoxia (5 hrs). Three varieties of tissue samples were analyzed (i) Freshly prepared tissue, used as control; (ii) cultures held under normoxic conditions and (iii) cultures exposed during cultivation to 5 h hypoxia. The gene expression was analyzed using the Affymetrix GeneChip RN-U34. The functional specificity of the cochlea regions are well reflected by the gene expression pattern. For example, the basal expression of Organ of Corti is characterized by genes involved in potassium and calcium homeostasis. The MOD is characterized by genes involved in regulation of maturation of neuronal cells. The SV is characterized by genes involved in ion homeostasis and blood flow. Cultivation dramatically changes the gene expression. In contrast, mild hypoxia showed only small changes. The changes are interpreted as stress response. We used this analysis as screening approach to detect significant changes in gene expression and used the RT-PCR analyses of independent sister cultures for confirmation. Correlation analysis showed close relations of the expression levels when aliquots of the biological material were compared. However, comparisons of the expression levels received by microarray and by RT-PCR analysis of independent sister samples resulted in 70-90 % in similar predictions. This data indicate that possible discrepancies has its basis in biological sampling rather than factors of methodical errors on the level of RT-PCR. Experiment Overall Design: Pooled samples of the following cochlea preparations were studied: Experiment Overall Design: (i) Native preparations of Organ of Corti, modiolus and stria vascularis from newborn rats used as controls; (ii) Organotypic cultures of these preparations under normoxic conditions (24 h); (iii) Cultures which were exposed to 5 h hypoxia during cultivation. Samples were collected for total RNA immediately after preparation of the inner ear structures (native samples) or 24 h after onset of cultivation (normoxia, hypoxia).

Dataset Information

Transcription profiling of rat hippocampus from young and aged rats with age-related spatial learning impairments

Publications

Changes in transcription within the CA1 field of the hippocampus are associated with age-related spatial learning impairments.

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