Genomic transcriptional profiling identifies candidates genes for successful aging
ABSTRACT: The inbred LOU/C/Jall rat is currently described as a model of successful aging. These rats have a longer healthy median lifespan than other strains, do not develop obesity, diabetes, or tumor and more importantly they do not show cognitive decline with aging. This is the first study to examine gene expression changes in the inbred LOU/C/Jall rat hippocampus and frontal cortex. Microarray data from LOU/C/Jall rats aged of 5 months were compared to the one measured in rats aged of 26 month. We have identified a set of 15 genes in the hippocampus and 70 genes in the frontal cortex that could be grouped into several clusters of similar expression profiles and that are involved in biological functions, namely regulation of plasticity, inflammatory response, metabolic, catabolic and homeostatic processes, and transcription. Genes were mainly up-regulated in aged brain. Gene expression profil in hippocampus and cortex frontal of LOU/C/Jall rats strain. Rats were 3 and 26 months old.
Project description:We used Affymetrix miRNA arrays to analyze the expression of miRNAs in the frontal cortex and hippocampus of 8-week-old C57BL/6J wt mice. We compared these microarray-based expression profiles to ones obtained by miRNA sequencing from the same brain regions of the same mouse strain. miRNA expression profiling of frontal cortex and hippocampus from C57BL/6J mice (N=3) was performed with Affymetrix miRNA array
Project description:This study investigated proteome profile in the hippocampus, medial prefrontal cortex (mPFC), and striatum of 14, 18, 23, and 27 months old rats in order to see the effect of aging on proteins in these regions. Using ultrahigh performance liquid chromatography coupled with Q Exactive HF Orbitrap mass spectrometry, we identified 1074 proteins in the hippocampus, 871 proteins in the mPFC, and 241 proteins the striatum. Ninety-seven, 25, and 5 of these proteins were differentially expressed with age in the hippocampus, mPFC, and striatum, respectively. Overall, aging causes divergent protein changes in specific brain regions, with the most prominent changes observed in the late-aged.
Project description:Curcumin has been demonstrated to have many neuroprotective properties, including improvement of cognition in humans and neurogenesis in animals, yet the mechanism of such effects remains unclear. Here, we assessed behavioural performance and hippocampal cell proliferation in aged rats after 6- and 12-week curcumin-fortified diets. Curcumin enhanced non-spatial and spatial memory, as well as dentate gyrate cell proliferation as compared to control diet rats. We also investigated underlying mechanistic pathways that might link curcumin treatment to increased cognition and neurogenesis via microarray analysis of cortical and hippocampal mRNA transcription. We used microarrays to investigate the effects of short-term (6-week) and long-term (12-week) curcumin-supplemented diet on gene expression of hippocampus and cortex in aged rats. The hippocampus and cortex of every three rats from one group were pooled together, respectively and used for RNA extraction and hybridization on Affymetrix microarrays. To ensure the reliability of the data, we conducted hybridization experiments in duplicate microarrays from each RNA sample. The tissues examined by microarray are as follows: the hippocampus and cortex of 6-week curcumin-treated 15-month-old rats, the hippocampus and cortex of 6-week no curcumin-treated 15-month-old rats (control rats), the hippocampus and cortex of 12-week curcumin-treated 15-month-old rats, the hippocampus and cortex of 12-week no curcumin-treated 15-month-old rats (control rats).
Project description:In order to elucidate the molecular mechanisms of action of Phenytoin, we examined by microarrays the effects of prolonged administration of Phenytoin on gene expression in hippocampus and frontal cortex of Sprague-Dawley rats chronically treated with Phenytoin.
Project description:To identify molecular pathological alterations in AD brains, we performed interspecies comparative microarray analyses using RNAs prepared from postmortem human brain tissues donated for the Hisayama study and hippocampal RNAs from the triple-transgenic mouse model of AD (3xTg-AD) Three-way ANOVA of microarray data from frontal cortex, temporal cortex and hippocampus with presence/absence of AD and vascular dementia, and sex, as factors revealed that the gene expression profile is most significantly altered in the hippocampi of AD brains. Comparative analyses of the brains of AD patients and a mouse model of AD showed that genes involved in non-insulin dependent DM and obesity were significantly altered in both, as were genes related to psychiatric disorders and Alzheimer’s disease. We prepared RNA samples from the gray matter of frontal and temporal cortices and hippocampi derived from 88 postmortem brains, among which 26 cases were pathologically diagnosed as having AD or an AD-like disorder. High-quality RNA (RIN≧6.9) samples were subjected to microarray analysis using the Affymetrix Human Gene 1.0 ST platform, and only those results that passed examinations for quality assurance and quality control of the Human Gene 1.0 ST arrays were retrieved. In total, we obtained gene expression profiles from the following samples: 33 frontal cortex samples, among which 15 were from AD patients; 29 temporal cortex samples, among which 10 were from AD patients; 17 hippocampus samples, among which seven were from AD patients
Project description:Patterns of gene expression in the aged entorhinal cortex and hippocampus were examined one month after entorhinal administration of BDNF lentivirus. Whole-genome patterns of expression were examined using Affymetrix arrays four weeks after entorhinal injection of lentiviral-BDNF or GFP injection compared to control subjects. Experiment Overall Design: 27 Samples total: 4 biological replicates of Age rats BDNF treated, 3 biological replicates of Age rats eGFP treated, and 4 biological replicates each of Aged and Young rats controls for the Entorhinal cortex tissue. 2 biological replicates of Age rats BDNF treated, 2 biological replicates of Age rats eGFP treated, and 4 biological replicates each of Age and Young rats controls for the hippocampus tissue.
Project description:MicroRNAs (miRNAs) are small regulatory molecules that cause post-transcriptional gene silencing. Although some miRNAs are known to have region-specific expression patterns in the adult brain, the functional consequences of the region-specificity to the gene regulatory networks of the brain nuclei are not clear. Therefore, we studied miRNA expression patterns by miRNA-seq in two brain regions, frontal cortex (FCx) and hippocampus (HP), which have separate biological functions. We identified 354 miRNA from FCx and 408 from HP. Several miRNA families and clusters were differentially expressed between FCx and HP, including the miR-8 family, miR-182|miR-96|miR-183 cluster, and miR-212|miR-312 cluster overexpressed in FCx and miR-34 family overexpressed in HP. To visualize the clusters, we developed support for viewing genomic alignments of miRNA-seq reads in the Chipster genome browser. We carried out pathway analysis of the predicted target genes of differentially expressed miRNA families and clusters to assess their putative biological functions. Interestingly, specific pathways were identified that are predicted to be regulated by several miRNAs from the same family/cluster. We have developed a miRNA-seq approach with a bioinformatic analysis workflow that is suitable for studying miRNA expression patterns from specific brain nuclei. FCx and HP were shown to have distinct miRNA expression patterns which were reflected in the predicted gene regulatory pathways. This methodology can be applied for the identification of brain region-specific and phenotype-specific miRNA-mRNA-regulatory networks from the adult and developing rodent brain. miRNA-seq of 3 replicates from frontal cortex, 3 replicates from hippocampus, and pooled sequence runs from both
Project description:Gene expression changes determine functional differentiation during development and are associated with functional decline during aging. While developmental changes are tightly regulated, regulation of aging changes is not well established. To assess the regulatory basis of age-related changes and investigate the mechanism of regulatory transition between development and aging, we measured mRNA and microRNA expression patterns in brains of humans and rhesus macaques over the entire species’ lifespan. We find that in both species, developmental and aging changes overlap in the course of lifetime with many changes found at the late age initiating in early childhood. Keywords: miRNA Age Series Keywords: Non-coding RNA profiling by high throughput sequencing rhesus macaque post-mortem brain samples from the superior frontal gyrus region of the prefrontal cortex were collected. The age ranges of the indibiual in rhesus macaque covered the whole life span fom newborn to death.
Project description:Effect of adjuvant dexamethasone treatment on gene expression in the hippocampus and cortex of control rats or rats suffering from pneumococcal meningitis which were sacrificed 72 h after infection.
Project description:This SuperSeries is composed of the following subset Series:; GSE14499: Effect of BDNF on the APP transgenic mouse model of Alzheimer's disease; GSE14505: Effect of BDNF on aging-related gene expression changes in young and aged rats Experiment Overall Design: Refer to individual Series