Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MRNA sequencing of two brain regions (prefrontal cortex and hippocampus) and left myocardial tissue in mice with chronic heart failure vs. sham-operated control mice

ABSTRACT: After induction of ischemic chronic heart failure (CHF), mice exhibited depression-like behavior, in terms of increased anhedonia, and decreased both exploratory activity and interest in novelty. On histology, ischemic CHF mice showed no alterations in overall cerebral morphology. To further evaluate relevant behavioral changes found in CHF mice, RNA-sequencing analysis of prefrontal cortex and hippocampus - the brain regions, whose structural and functional alterations are associated with an increased risk for developing major depressive disorder - and of left myocardial tissue was performed in CHF vs. sham-operated animals. RNA-sequencing revealed relevant changes in hippocampal or prefrontal cortical expression of genes responsible for axonal vesicle transport (Kif5b), signal transduction (Arc, Gabrb2), limitation of inflammation (RORA; Nr4a1) and of hypoxic brain damage (Hif3a). Besides, the actual literature describes some of the genes (RORA, Gabrb2, Npas4, and Junb) being associated with depression-like behavior. Nr4a1 significantly regulated in both brain and heart tissue after induction of ischemic CHF could be a potential link and reveals the central role of inflammation in the interrelation of the brain and the failing heart. Heart failure vs. sham-operation were performed in C57BL/6 male mice. After development of chronic heart failure (CHF) 8 weeks after the operation RNA was extracted out of prefrontal cortex, hippocampus and left ventricular myocardium in both groups. RNA of 3 ischemic CHF mice versus 6 sham operated mice was pooled and further subjected to RNA sequencing. To fabricate singular pools each probe of the group equally contributed with the final amount of 2 µg RNA per pool with the result that we had 6 different pools to be further evaluated. The mRNA profile was generated by IGA Technology, Italy (http://www.igatechnology.com/) by deep sequencing, using Illumina HiSeq 2000 platform (HiSeq). CLC-Bio Genomics Workbench software (CLC Bio, Denmark) was used to calculate gene expression levels based on Mortazavi et al. (Nat Methods. 2008;5:621-628) approach.

ORGANISM(S): Mus musculus

SUBMITTER: Anna Frey

PROVIDER: E-GEOD-55280 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Experimental heart failure causes depression-like behavior together with differential regulation of inflammatory and structural genes in the brain.

Frey Anna A Popp Sandy S Post Antonia A Langer Simon S Lehmann Marc M Hofmann Ulrich U Sirén Anna-Leena AL Hommers Leif L Schmitt Angelika A Strekalova Tatyana T Ertl Georg G Lesch Klaus-Peter KP Frantz Stefan S

Frontiers in behavioral neuroscience 20141031

<h4>Background</h4>Depression and anxiety are common and independent outcome predictors in patients with chronic heart failure (CHF). However, it is unclear whether CHF causes depression. Thus, we investigated whether mice develop anxiety- and depression-like behavior after induction of ischemic CHF by myocardial infarction (MI).<h4>Methods and results</h4>In order to assess depression-like behavior, anhedonia was investigated by repeatedly testing sucrose preference for 8 weeks after coronary a ...[more]

PMID: 25400562

Similar Datasets

Project description:Impaired resistance to insulin, the key defect in type 2 diabetes (T2D), is associated with a low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic inflexibility. The hampered metabolic adaptability triggers a further damage of insulin signaling. Since skeletal muscle is the main site of glucose uptake, effectiveness of T2D treatment depends in large on the improvement of insulin sensitivity and metabolic adaptability of the muscle. We have shown previously in mice fed an obesogenic high-fat diet that a combination treatment using n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and thiazolidinedione (TZD) anti-diabetic drugs preserved metabolic health and synergistically improved muscle insulin sensitivity. We investigated here whether TZD rosiglitazone could elicit the additive beneficial effects on metabolic flexibility when combined with n-3 LC-PUFA. Adult male C57BL/6N mice were fed an obesogenic corn oil-based high-fat diet (cHF) for 8 weeks, or randomly assigned to various dietary treatments: (i) cHF+F, cHF with n-3 LC-PUFA concentrate replacing 15% of dietary lipids; (ii) cHF+ROSI, cHF with 10 mg rosiglitazone/kg diet; and (iii) cHF+F+ROSI, or chow-fed. Indirect calorimetry demonstrated superior preservation of metabolic flexibility to carbohydrates in response to the combination treatment. Metabolomic and gene expression analyses in the muscle suggested distinct and complementary effects of the single treatments, with rosiglitazone augmenting insulin sensitivity by the modulation of branched-chain amino acid metabolism, and n-3 LC PUFA supporting complete oxidation of fatty acids in mitochondria. These beneficial metabolic effects were associated with the activation of the switch between glycolytic and oxidative muscle fibers, especially in the cHF+F+ROSI mice. Our results further support the idea that the combination treatment using n-3 LC-PUFA and TZDs could improve the efficacy of the treatment of obese and diabetic patients. Male C57BL/6N mice had free access to water and Chow. Three-month-old mice were randomly assigned (8 animals per group) to cHF diet (lipid content ~35% wt/wt) or to the following 'treatments' by isocaloric cHF-based diets, namely (i) cHF+F, cHF diet supplemented with n-3 LC-PUFA concentrate (46% DHA, 14% EPA, wt/wt, as triglycerides; product EPAX 1050 TG), which replaced 15% wt/wt of dietary lipids; (ii) cHF+ROSI, cHF diet supplemented with 10 mg rosiglitazone/kg diet; and (iii) cHF+F+ROSI, cHF diet supplemented with both n-3 LC-PUFA concentrate and rosiglitazone. cHF+ROSI at a higher dose, namely 100 mg rosiglitazone/kg diet was also included in the study, but not in the final microarray analysis. The treatment lasted for 8 weeks, whereafter the animals were first fasted for 10 hours during the light phase of the day (between 8.00hr and 18.00hr), than re-fed Chow (starting at 18.00hr), and killed the following day by cervical dislocation under pentobarbital anesthesia (between 9.00hr and 11.00hr); the so-called 'diet-switch protocol'. Gastrocnemius muscle was isolated and used for total RNA isolation.

Dataset Information

MRNA sequencing of two brain regions (prefrontal cortex and hippocampus) and left myocardial tissue in mice with chronic heart failure vs. sham-operated control mice

Publications

Experimental heart failure causes depression-like behavior together with differential regulation of inflammatory and structural genes in the brain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets