Transcription profiling of rat heart ventricle samples from animals subjected to differing exercise regimes
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Natalie Schweitzer
PROVIDER: E-GEOD-5085 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The rates of obesity and sedentary lifestyle are on a dramatic incline, with associated detrimental health effects among women in particular. Although exercise prescriptions are useful for overcoming these problems, success can be hampered by differential responsiveness among individuals in cardiovascular fitness indices (i.e., improvements in strength, lipids, VO2max). Genetic factors appear to play an important role in determining this inter-individual variation in responsiveness. We performed microarray analyses on mRNA in whole blood from 60 sedentary women from a multi-ethnic cohort who underwent 12 weeks of exercise, to identify gene subsets that were differentially expressed between individuals who experienced the greatest and least improvements in fitness based upon a composite fitness score index. We identified 43 transcripts in 39 unique genes (FDR<10%; FC>1.5) whose expression increased the most in “high” versus “low” premenopausal female responders. Several (TIGD7, UQCRH, PSMA6, WDR12, TFB2M, USP15) have reported associations with fitness-related phenotypes. Bioinformatic analysis of the 39 genes identified 4 miRNAs whose expression has been linked to cardiovascular diseases (ANKRD22: miR-637, LRRFIP1: miR-132, PRKAR2B: miR-92a, RSAD2:miR-192). These 39 genes were enriched in 6 biological pathways, including the oxidative phosphorylation pathway (p=8.08 x 10-3). Two genes, LRRFIP1 and SNORD30, were also identified with lower expression in high responding postmenopausal women. In summary, we identified gene signatures based on mRNA analysis that define responsiveness to exercise in a largely minority-based female cohort. Importantly, this study validates several genes/pathways previously associated with exercise responsiveness and extends these findings with additional novel genes. We performed microarray analyses on mRNA in whole blood from 60 sedentary women from a multi-ethnic cohort who underwent 12 weeks of exercise, to identify gene subsets that were differentially expressed between individuals who experienced the greatest and least improvements in fitness based upon a composite fitness score index.
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Project description:Exercise improves brain function enhancing neuronal plasticity and cognitive enhancement. For voluntary resistance wheel running (RWR) exercise, with a load of 30% of body weight, we reported enhancement of neurogenesis and spatial memory associated with hippocampal brain-derived neurotrophic factor (BDNF) signaling compared to wheel running (WR) without a load (Lee et al., 2012; Lee et al., 2013). Despite these new evidences, mechanisms for RWR-induced improvement of hippocampal function remained to be clarified. In the present study, we have utilized the high-throughput DNA microarray approach to gain deep insight into molecular mechanisms underlying these changes that could be novel targets of RWR-induced hippocampal plasticity. To do so, whole genome (4x44K) high-density oligonucleotide microarrays were used to monitor the expression level of gene transcripts in the hippocampus of rats voluntary running for 4 weeks in comparison with sedentary animals. These rats showed a significant decrease in average running distance although average work levels immensely increased 12-fold in the RWR group, resulting in muscular adaptation for the fast-twitch plantaris muscle. DNA microarray analysis revealed that 122 (sedentary x WR) and 157 (sedentary x RWR) genes were up-regulated (> 1.5-fold change) as compared with 97 (sedentary x WR) and 467 (sedentary x RWR) down-regulated genes (< 0.75-fold change). Functional categorization using the Ingenuity Pathway Analysis (IPA) revealed expression pattern changes in the major categories of disease and disorders, molecular functions and physiological system development and function. Among these, RWR up-regulated genes such as NFATc1, AVPR1A and FGFR4, which are crucial role for neuronal development and its functions. The down-regulated inflammatory cytokines (IL1B, IL10, IL2RA, TNF) and chemokines (CXCL1, CXCL9, CXCL10, CCL2, CCL13, CCR4) might be important to neuronal dysfunction and vulnerability. Taken together, these gene candidates are suggested to play a critical role in hippocampal plasticity. This is a first study presenting not only new information into the voluntary RWR influenced transcriptome in the rat hippocampus, but also provides a hypothesis for the RWR influenced enhancement in brain function. 10-week-old male Wistar rats were randomly allocated to three groups: (1) housed in standard cages and used as non-active controls (sedentary, n = 10), (2) wheel running with no resistance (WR, n = 8), and (3) housed in cages with resistance running wheels with an adjustable resistance (RWR, n = 8). Rats of both running wheel groups (WR and RWR) were housed individually and had free access to a specially designed running wheel apparatus for 24 h/day. Between 08:00 and 12:00 on the day after the final day of exercise, the animals were immediately decapitated using a guillotine. The hippocampi were rapidly dissected, snap frozen in liquid nitrogen and stored at —80°C prior to further analysis. The deep-frozen hippocampi were transferred to a precooled (in liquid nitrogen) mortar and ground with a pestle to a very fine powder with liquid nitrogen. Total RNA was extracted and validated followed by checking subsequently synthesized cDNA by RT-PCR. A rat 4x44K whole genome oligo DNA microarray chip was used for global gene expression analysis using the hippocampi. Fluorescently labeled targets of Sed, WR and RWR samples were hybridized to the same microarray slide with 60-mer probes. A flip labeling (dye swap or reverse labeling with Cy3 and Cy5 dyes) procedure was followed to nullify the dye bias associated with unequal incorporation of the two Cy dyes into cDNA. Briefly, to select differentially expressed genes, we identified genes that were up regulated in chip 1 (Cy3/Cy5 label for sedentary and WR, respectively) but down regulated in chip 2 (Cy3/Cy5 label for WR and sedentary, respectively) for the hippocampus. The same selection criteria were applied for chips 3-4 (sedentary and RWR). Hybridization and wash processes were performed according to the manufacturer’s instructions, and hybridized microarrays were scanned using an agilent microarray scanner. The functional and network analysis were generated through the use of IPA (Ingenuity® Systems, www.ingenuity.com). To validate gene changes in array data and test the BDNF signaling-related molecules and expression of select transcripts were determined by quantitative real-time RT-PCR.
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