{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bruns B"],"funding":["Medizinische Fakultät Heidelberg der Universität Heidelberg","Deutsche Forschungsgemeinschaft","German Ministry of Education and Research","German Centre for Cardiovascular Research"],"pagination":["44"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9448693"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["117(1)"],"pubmed_abstract":["Myocardial infarction (MI) with subsequent depression is associated with increased cardiac mortality. Impaired central mineralocorticoid (MR) and glucocorticoid receptor (GR) equilibrium has been suggested as a key mechanism in the pathogenesis of human depression. Here, we investigate if deficient central MR/GR signaling is causative for a poor outcome after MI in mice. Mice with an inducible forebrain-specific MR/GR knockout (MR/GR-KO) underwent baseline and follow-up echocardiography every 2 weeks after MI or sham operation. Behavioral testing at 4 weeks confirmed significant depressive-like behavior and, strikingly, a higher mortality after MI, while cardiac function and myocardial damage remained unaffected. Telemetry revealed cardiac autonomic imbalance with marked bradycardia and ventricular tachycardia (VT) upon MI in MR/GR-KO. Mechanistically, we found a higher responsiveness to atropine, pointing to impaired parasympathetic tone of 'depressive' mice after MI. Serum corticosterone levels were increased but-in line with the higher vagal tone-plasma and cardiac catecholamines were decreased. MR/GR deficiency in the forebrain led to significant depressive-like behavior and a higher mortality after MI. This was accompanied by increased vagal tone, depleted catecholaminergic compensatory capacity and VTs. Thus, limbic MR/GR disequilibrium may contribute to the impaired outcome of depressive patients after MI and possibly explain the lack of anti-depressive treatment benefit."],"journal":["Basic research in cardiology"],"pubmed_title":["Forebrain corticosteroid receptors promote post-myocardial infarction depression and mortality."],"pmcid":["PMC9448693"],"funding_grant_id":["SFB 1118","project number 236360313"],"pubmed_authors":["Bruns B","Schmitz T","Dewenter M","Frey N","Friederich HC","Hamze-Sinno M","Herzog W","Spaich S","Daub R","Backs J","Katus H","Schultz JH","Schwale C","Gass P","Vogt M"],"additional_accession":[]},"is_claimable":false,"name":"Forebrain corticosteroid receptors promote post-myocardial infarction depression and mortality.","description":"Myocardial infarction (MI) with subsequent depression is associated with increased cardiac mortality. Impaired central mineralocorticoid (MR) and glucocorticoid receptor (GR) equilibrium has been suggested as a key mechanism in the pathogenesis of human depression. Here, we investigate if deficient central MR/GR signaling is causative for a poor outcome after MI in mice. Mice with an inducible forebrain-specific MR/GR knockout (MR/GR-KO) underwent baseline and follow-up echocardiography every 2 weeks after MI or sham operation. Behavioral testing at 4 weeks confirmed significant depressive-like behavior and, strikingly, a higher mortality after MI, while cardiac function and myocardial damage remained unaffected. Telemetry revealed cardiac autonomic imbalance with marked bradycardia and ventricular tachycardia (VT) upon MI in MR/GR-KO. Mechanistically, we found a higher responsiveness to atropine, pointing to impaired parasympathetic tone of 'depressive' mice after MI. Serum corticosterone levels were increased but-in line with the higher vagal tone-plasma and cardiac catecholamines were decreased. MR/GR deficiency in the forebrain led to significant depressive-like behavior and a higher mortality after MI. This was accompanied by increased vagal tone, depleted catecholaminergic compensatory capacity and VTs. Thus, limbic MR/GR disequilibrium may contribute to the impaired outcome of depressive patients after MI and possibly explain the lack of anti-depressive treatment benefit.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2025-04-19T20:34:15.665Z","creation":"2025-02-18T23:49:17.567Z"},"accession":"S-EPMC9448693","cross_references":{"pubmed":["36068417"],"doi":["10.1007/s00395-022-00951-6"]}}