Dataset Information

Differential proteomics of the synaptosomal fraction from rat dentate gyrus identified the changes associated with aging-dependent cognitive decline

ABSTRACT: The study contained three groups of Sprague-Dawley male rats – two groups of aging animals (22-24 months) separated based on performance in spatial reference memory task; and the third, control group of young animals () not separated by behavioural testing. The synaptosome – enriched membrane fraction of the dentate gyrus was isolated from nine randomly chosen individuals per group and analysed by tandem mass tag (TMT) labelling and mass spectrometry (MS)-based quantitative proteomics. The proteomic experiment was performed in three TMT10plex sets, with each set containing samples from three biological replicates per group and one TMT 126 reference channel reserved to directly compare the protein intensities across the entire study. The peptides were analysed in two parallel MS runs representing two technical replicates per biological sample. The total number of 6513 protein entries was identified of which 471 showed a significantly changed level (p<0.05) in any of the three animal groups. The comparison between aged and young animals revealed 293 significantly changed proteins (p<0.05) in aged good performers vs young rats, and 310 significant proteins (p < 0.05) in aged bad performers vs young ones. The proteomic differences between aged good vs bad performers were represented by 78 significantly changed proteins (p < 0.05).

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Dentate Gyrus, Dentate Gyrus Of Hippocampal Formation

SUBMITTER: Gert Lubec

LAB HEAD: Gert Lubec

PROVIDER: PXD013172 | Pride | 2019-08-19

REPOSITORIES: Pride

ACCESS DATA

Publications

Dentate Gyrus Peroxiredoxin 6 Levels Discriminate Aged Unimpaired From Impaired Rats in a Spatial Memory Task.

Lubec Jana J Smidak Roman R Malikovic Jovana J Feyissa Daniel Daba DD Korz Volker V Höger Harald H Lubec Gert G

Frontiers in aging neuroscience 20190731

Similar to humans, the normal aged rat population is not homogeneous in terms of cognitive function. Two distinct subpopulations of aged Sprague-Dawley rats can be identified on the basis of spatial memory performance in the hole-board paradigm. It was the aim of the study to reveal protein changes relevant to aging and spatial memory performance. Aged impaired (AI) and unimpaired (AU) male rats, 22-24 months old were selected from a large cohort of 160 animals; young animals served as control. ...[more]

PMID: 31417400

Similar Datasets

Project description:We performed a microarray analysis of auditory midbrain (inferior colliculus, IC) mRNA from young adult CBA mice (controls) with good hearing, middle aged (MA) with good hearing, and old mild (MP) and severe (SP) presbycusic CBA mice. Fold Change data derived from RMA normalization revealed that the overall GABA receptor alpha 6 expression profiles for MA, MP and SP were down-regulated relative to young adult controls with good hearing. Relative real-time PCR for five GABA receptors confirmed this age-related down regulation quantitatively. Functional hearing data: Auditory Brainstem Responses (ABR) enriched the analysis to select the probe-sets that changed with age and hearing loss by the linear regression best-fit line model technique. GABA receptor genotype-phenotype correlations with auditory functional data indicated that GABA-receptor subtypes are under expressed in SP mice. Hierarchical clustering (HC) analyses yielded statistical significance of normalized GeneChip data Real-time PCR showed that Gabra6, GABA B receptor 1 (Gabbr1), and Gaba transporter protein Slc32a1 may be involved in physiological changes that occur in age-related hearing loss. Presbycusis – age-related hearing loss – is the number one communicative disorder of our aged population. In this study we analyzed gene expression for a set of GABA receptors in the inferior colliculus of aging CBA mice using the Affymetrix GeneChip MOE430A. Functional phenotypic hearing changes from RMA normalized microarray data (39 replicates) in four age-groups, Young Controls and Middle aged mice with good hearing, mild and sever e presbycusis from old mice. Fold change gene expression derived from RMA normalized data were first subjected to one-way ANOVA, and then linear regression was performed. The selected gene expression changes were confirmed by relative real-time relative to young adult controls with good hearing. Statistically significant and real time PCR confirmed GABA receptor genes; Gabra6, GABA B receptor 1 (Gabbr1), and Gaba transporter protein Slc32a1, may be involved in physiological changes that occur in age-related hearing loss. Lastly, gene expression measures of each age group were correlated with pathway/network relationships relevant to the inferior colliculus using Pathway Architect, to identify key pathways consistent with the gene expression changes observed In the study of Expression changes in IC GABA receptors in the Auditory Midbrain of young adult and aging presbycusis mice total of thirty nine chips were used. The normal aging mice were in Four groups Young adults Controls with good hearing (8 mice, 8 MOE430A GeneChips), Middle aged group with good hearing ( 17 mice, 17 MOE430A GeneChips), Mild Presbycusis with limited hearing loss (9 mice, 9 MOE430A GeneChips) and Severe Presbycusis (5 mice, 5 MOE430A GeneChips).

Project description:Adult aging is a complex biological process associated with altered gene expression and a decline in physiological performance. The microRNAs have been implicated in cardiac development, cardiac hypertrophy and heart failure. However, the impact of adult aging on cardiac expression of both miRNA guide strand (miR) and passenger strand (miR*), as well as miRNA clusters have not been well established. We explored the expression profile of both miR and miR* in the heart. We found that 65 miRNAs were differentially expressed in old versus young adult heart; approximately half of them were clustered miRNAs that were distributed in 11 miRNA clusters. Each miRNA cluster contains from 2 to as many as 71 miRNA genes. The majority of the clusters displayed unified expression, with most cluster members within a cluster being either increased or decreased together, suggesting that most clusters are regulated by a common signaling mechanism and that the combined expression of multiple miRNA genes in a cluster could pose an impact on a broad range of targets during aging. We also found age-related changes in the expression of miR*s. Bioinformatic analysis revealed that miR-21 and miR-21* had their own silencing targets. The expression of both miR and miR* correlated with that of pri-miRNA transcript over the time course from development and maturation through adult aging. Age-related changes in the expression of Ago1 and Ago2 proteins in the heart were also observed. Our data suggest that a concert of effects, including transcriptional regulation of pri-miRNA transcript and altered expression of Argonaut proteins, contribute to age-related changes in the expression of both miR and miR* strands during adult aging. The major changes occurred later in life, from middle to old age. It is likely that the expression of both miR and miR* is regulated by transcription and Ago1 and Ago2 proteins. Six healthy C57BL/6 mice were used in this study. Three of them were 4 months old (young adult mice: YA), and the other three were 24 months old (old mice). Total RNA samples were isolated from mouse hearts and then shipped to Exiqon Inc., where microRNA array analysis was performed. Three array slides were used for the hybridization. Each array slide hybridized with two samples labeld with either Hy3 or Hy5, with array #1 being hybridized with samples YA-1 (Hy3) and Old-1 (Hy5), array #2 with samples YA-2 (Hy3) and Old-2 (Hy5) and array #3 with samples YA-3 (Hy5) and Old-3 (Hy3). In our publication, we reveal the detail of the experiment and statistical analysis that were provided by Exiqon Inc.

Dataset Information

Differential proteomics of the synaptosomal fraction from rat dentate gyrus identified the changes associated with aging-dependent cognitive decline

Publications

Dentate Gyrus Peroxiredoxin 6 Levels Discriminate Aged Unimpaired From Impaired Rats in a Spatial Memory Task.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure