Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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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

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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]

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