Forebrain corticosteroid receptors promote post-myocardial infarction depression and mortality.
Depression
Glucocorticoid receptor
Heart failure
Limbic system
Mineralocorticoid receptor
Myocardial infarction
Journal
Basic research in cardiology
ISSN: 1435-1803
Titre abrégé: Basic Res Cardiol
Pays: Germany
ID NLM: 0360342
Informations de publication
Date de publication:
06 09 2022
06 09 2022
Historique:
received:
16
02
2022
accepted:
07
08
2022
revised:
19
07
2022
entrez:
6
9
2022
pubmed:
7
9
2022
medline:
9
9
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36068417
doi: 10.1007/s00395-022-00951-6
pii: 10.1007/s00395-022-00951-6
pmc: PMC9448693
doi:
Substances chimiques
Receptors, Glucocorticoid
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
44Informations de copyright
© 2022. The Author(s).
Références
Abelaira HM, Reus GZ, Quevedo J (2013) Animal models as tools to study the pathophysiology of depression. Rev Bras Psiquiatr 35(Suppl 2):S112-120. https://doi.org/10.1590/1516-4446-2013-1098
doi: 10.1590/1516-4446-2013-1098
Akiyama T, Yamazaki T, Ninomiya I (1993) Differential regional responses of myocardial interstitial noradrenaline levels to coronary occlusion. Cardiovasc Res 27:817–822. https://doi.org/10.1093/cvr/27.5.817
doi: 10.1093/cvr/27.5.817
Arriza JL, Simerly RB, Swanson LW, Evans RM (1988) The neuronal mineralocorticoid receptor as a mediator of glucocorticoid response. Neuron 1:887–900. https://doi.org/10.1016/0896-6273(88)90136-5
doi: 10.1016/0896-6273(88)90136-5
Backs J, Haunstetter A, Gerber SH, Metz J, Borst MM, Strasser RH, Kübler W, Haass M (2001) The neuronal norepinephrine transporter in experimental heart failure: evidence for a posttranscriptional downregulation. J Mol Cell Cardiol 33:461–472. https://doi.org/10.1006/jmcc.2000.1319
doi: 10.1006/jmcc.2000.1319
Bauer A (2017) Identifying high-risk post-infarction patients by autonomic testing—below the tip of the iceberg. Int J Cardiol 237:19–21. https://doi.org/10.1016/j.ijcard.2017.03.087
doi: 10.1016/j.ijcard.2017.03.087
Berger S, Wolfer DP, Selbach O, Alter H, Erdmann G, Reichardt HM, Chepkova AN, Welzl H, Haas HL, Lipp HP, Schutz G (2006) Loss of the limbic mineralocorticoid receptor impairs behavioral plasticity. Proc Natl Acad Sci USA 103:195–200. https://doi.org/10.1073/pnas.0503878102
doi: 10.1073/pnas.0503878102
Boyle MP, Brewer JA, Funatsu M, Wozniak DF, Tsien JZ, Izumi Y, Muglia LJ (2005) Acquired deficit of forebrain glucocorticoid receptor produces depression-like changes in adrenal axis regulation and behavior. Proc Natl Acad Sci USA 102:473–478. https://doi.org/10.1073/pnas.0406458102
doi: 10.1073/pnas.0406458102
Brown MR, Fisher LA (1986) Glucocorticoid suppression of the sympathetic nervous system and adrenal medulla. Life Sci 39:1003–1012. https://doi.org/10.1016/0024-3205(86)90289-4
doi: 10.1016/0024-3205(86)90289-4
Bruns B, Schmitz T, Diemert N, Schwale C, Werhahn SM, Weyrauther F, Gass P, Vogt MA, Katus H, Herzog W, Backs J, Schultz JH (2019) Learned helplessness reveals a population at risk for depressive-like behaviour after myocardial infarction in mice. ESC Heart Fail 6:711–722. https://doi.org/10.1002/ehf2.12440
doi: 10.1002/ehf2.12440
de Kloet ER, Derijk RH, Meijer OC (2007) Therapy Insight: is there an imbalanced response of mineralocorticoid and glucocorticoid receptors in depression? Nat Clin Pract Endocrinol Metab 3:168–179. https://doi.org/10.1038/ncpendmet0403
doi: 10.1038/ncpendmet0403
De Villiers C, Riley PR (2020) Mouse models of myocardial infarction: comparing permanent ligation and ischaemia-reperfusion. Dis Model Mech. https://doi.org/10.1242/dmm.046565
doi: 10.1242/dmm.046565
Erdmann G, Schutz G, Berger S (2007) Inducible gene inactivation in neurons of the adult mouse forebrain. BMC Neurosci 8:63. https://doi.org/10.1186/1471-2202-8-63
doi: 10.1186/1471-2202-8-63
Francis J, Weiss RM, Wei SG, Johnson AK, Beltz TG, Zimmerman K, Felder RB (2001) Central mineralocorticoid receptor blockade improves volume regulation and reduces sympathetic drive in heart failure. Am J Physiol Heart Circ Physiol 281:H2241-2251. https://doi.org/10.1152/ajpheart.2001.281.5.H2241
doi: 10.1152/ajpheart.2001.281.5.H2241
Frasure-Smith N, Lesperance F (2003) Depression and other psychological risks following myocardial infarction. Arch Gen Psychiatry 60:627–636. https://doi.org/10.1001/archpsyc.60.6.627
doi: 10.1001/archpsyc.60.6.627
Frasure-Smith N, Lesperance F, Talajic M (1995) Depression and 18-month prognosis after myocardial infarction. Circulation 91:999–1005. https://doi.org/10.1161/01.cir.91.4.999
doi: 10.1161/01.cir.91.4.999
Frasure-Smith N, Lesperance F, Irwin MR, Sauve C, Lesperance J, Theroux P (2007) Depression, C-reactive protein and two-year major adverse cardiac events in men after acute coronary syndromes. Biol Psychiatry 62:302–308. https://doi.org/10.1016/j.biopsych.2006.09.029
doi: 10.1016/j.biopsych.2006.09.029
Frey A, Popp S, Post A, Langer S, Lehmann M, Hofmann U, Siren AL, Hommers L, Schmitt A, Strekalova T, Ertl G, Lesch KP, Frantz S (2014) Experimental heart failure causes depression-like behavior together with differential regulation of inflammatory and structural genes in the brain. Front Behav Neurosci 8:376. https://doi.org/10.3389/fnbeh.2014.00376
doi: 10.3389/fnbeh.2014.00376
Gomez Sanchez EP (2009) Central mineralocorticoid receptors and cardiovascular disease. Neuroendocrinology 90:245–250. https://doi.org/10.1159/000227807
doi: 10.1159/000227807
Gourine A, Gourine AV (2014) Neural mechanisms of cardioprotection. Physiology (Bethesda) 29:133–140. https://doi.org/10.1152/physiol.00037.2013
doi: 10.1152/physiol.00037.2013
Grippo AJ, Santos CM, Johnson RF, Beltz TG, Martins JB, Felder RB, Johnson AK (2004) Increased susceptibility to ventricular arrhythmias in a rodent model of experimental depression. Am J Physiol Heart Circ Physiol 286:H619-626. https://doi.org/10.1152/ajpheart.00450.2003
doi: 10.1152/ajpheart.00450.2003
Hånell A, Marklund N (2014) Structured evaluation of rodent behavioral tests used in drug discovery research. Front Behav Neurosci 8:252–252. https://doi.org/10.3389/fnbeh.2014.00252
doi: 10.3389/fnbeh.2014.00252
Harris AP, Holmes MC, de Kloet ER, Chapman KE, Seckl JR (2013) Mineralocorticoid and glucocorticoid receptor balance in control of HPA axis and behaviour. Psychoneuroendocrinology 38:648–658. https://doi.org/10.1016/j.psyneuen.2012.08.007
doi: 10.1016/j.psyneuen.2012.08.007
Hayano J, Yuda E (2019) Pitfalls of assessment of autonomic function by heart rate variability. J Physiol Anthropol 38:3. https://doi.org/10.1186/s40101-019-0193-2
doi: 10.1186/s40101-019-0193-2
Hayano J, Sakakibara Y, Yamada A, Yamada M, Mukai S, Fujinami T, Yokoyama K, Watanabe Y, Takata K (1991) Accuracy of assessment of cardiac vagal tone by heart rate variability in normal subjects. Am J Cardiol 67:199–204. https://doi.org/10.1016/0002-9149(91)90445-q
doi: 10.1016/0002-9149(91)90445-q
Hayano J, Mukai S, Sakakibara M, Okada A, Takata K, Fujinami T (1994) Effects of respiratory interval on vagal modulation of heart rate. Am J Physiol 267:H33-40. https://doi.org/10.1152/ajpheart.1994.267.1.H33
doi: 10.1152/ajpheart.1994.267.1.H33
Heusch G (2017) Vagal cardioprotection in reperfused acute myocardial infarction. JACC Cardiovasc Interv 10:1521–1522. https://doi.org/10.1016/j.jcin.2017.05.063
doi: 10.1016/j.jcin.2017.05.063
Heusch G, Deussen A, Thämer V (1985) Cardiac sympathetic nerve activity and progressive vasoconstriction distal to coronary stenoses: feed-back aggravation of myocardial ischemia. J Auton Nerv Syst 13:311–326. https://doi.org/10.1016/0165-1838(85)90020-7
doi: 10.1016/0165-1838(85)90020-7
Holsboer F (2000) The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 23:477–501. https://doi.org/10.1016/S0893-133X(00)00159-7
doi: 10.1016/S0893-133X(00)00159-7
Howell MP, Muglia LJ (2006) Effects of genetically altered brain glucocorticoid receptor action on behavior and adrenal axis regulation in mice. Front Neuroendocrinol 27:275–284. https://doi.org/10.1016/j.yfrne.2006.05.001
doi: 10.1016/j.yfrne.2006.05.001
Huffman JC, Celano CM, Beach SR, Motiwala SR, Januzzi JL (2013) Depression and cardiac disease: epidemiology, mechanisms, and diagnosis. Cardiovasc Psychiatry Neurol 2013:695925. https://doi.org/10.1155/2013/695925
doi: 10.1155/2013/695925
Kollai M, Koizumi K (1979) Reciprocal and non-reciprocal action of the vagal and sympathetic nerves innervating the heart. J Auton Nerv Syst 1:33–52. https://doi.org/10.1016/0165-1838(79)90004-3
doi: 10.1016/0165-1838(79)90004-3
Kop WJ, Synowski SJ, Gottlieb SS (2011) Depression in heart failure: biobehavioral mechanisms. Heart Fail Clin 7:23–38. https://doi.org/10.1016/j.hfc.2010.08.011
doi: 10.1016/j.hfc.2010.08.011
Kretz O, Schmid W, Berger S, Gass P (2001) The mineralocorticoid receptor expression in the mouse CNS is conserved during development. NeuroReport 12:1133–1137. https://doi.org/10.1097/00001756-200105080-00017
doi: 10.1097/00001756-200105080-00017
Kristen AV, Kreusser MM, Lehmann L, Kinscherf R, Katus HA, Haass M, Backs J (2006) Preserved norepinephrine reuptake but reduced sympathetic nerve endings in hypertrophic volume-overloaded rat hearts. J Card Fail 12:577–583. https://doi.org/10.1016/j.cardfail.2006.05.006
doi: 10.1016/j.cardfail.2006.05.006
Kuroko Y, Yamazaki T, Tokunaga N, Akiyama T, Kitagawa H, Ishino K, Sano S, Mori H (2007) Cardiac epinephrine synthesis and ischemia-induced myocardial epinephrine release. Cardiovasc Res 74:438–444. https://doi.org/10.1016/j.cardiores.2007.02.018
doi: 10.1016/j.cardiores.2007.02.018
Kvetnansky R, Pacak K, Fukuhara K, Viskupic E, Hiremagalur B, Nankova B, Goldstein DS, Sabban EL, Kopin IJ (1995) Sympathoadrenal system in stress. Interaction with the hypothalamic-pituitary-adrenocortical system. Ann N Y Acad Sci 771:131–158. https://doi.org/10.1111/j.1749-6632.1995.tb44676.x
doi: 10.1111/j.1749-6632.1995.tb44676.x
McIlwain KL, Merriweather MY, Yuva-Paylor LA, Paylor R (2001) The use of behavioral test batteries: effects of training history. Physiol Behav 73:705–717
doi: 10.1016/S0031-9384(01)00528-5
Oitzl MS, Champagne DL, van der Veen R, de Kloet ER (2010) Brain development under stress: hypotheses of glucocorticoid actions revisited. Neurosci Biobehav Rev 34:853–866. https://doi.org/10.1016/j.neubiorev.2009.07.006
doi: 10.1016/j.neubiorev.2009.07.006
Okada S, Yokoyama M, Toko H, Tateno K, Moriya J, Shimizu I, Nojima A, Ito T, Yoshida Y, Kobayashi Y, Katagiri H, Minamino T, Komuro I (2012) Brain-derived neurotrophic factor protects against cardiac dysfunction after myocardial infarction via a central nervous system-mediated pathway. Arterioscler Thromb Vasc Biol 32:1902–1909. https://doi.org/10.1161/ATVBAHA.112.248930
doi: 10.1161/ATVBAHA.112.248930
Paton JF, Boscan P, Pickering AE, Nalivaiko E (2005) The yin and yang of cardiac autonomic control: vago-sympathetic interactions revisited. Brain Res Brain Res Rev 49:555–565. https://doi.org/10.1016/j.brainresrev.2005.02.005
doi: 10.1016/j.brainresrev.2005.02.005
Plaschke K, Feindt J, Djuric Z, Heiland S, Autschbach F, Lewicka S, Martin E, Bardenheuer HJ, Nawroth PP, Bierhaus A (2006) Chronic corticosterone-induced deterioration in rat behaviour is not paralleled by changes in hippocampal NF-kappaB-activation. Stress 9:97–106. https://doi.org/10.1080/10253890600691551
doi: 10.1080/10253890600691551
Ridder S, Chourbaji S, Hellweg R, Urani A, Zacher C, Schmid W, Zink M, Hortnagl H, Flor H, Henn FA, Schutz G, Gass P (2005) Mice with genetically altered glucocorticoid receptor expression show altered sensitivity for stress-induced depressive reactions. J Neurosci 25:6243–6250. https://doi.org/10.1523/JNEUROSCI.0736-05.2005
doi: 10.1523/JNEUROSCI.0736-05.2005
Rossier MF, Python M, Maturana AD (2010) Contribution of mineralocorticoid and glucocorticoid receptors to the chronotropic and hypertrophic actions of aldosterone in neonatal rat ventricular myocytes. Endocrinology 151:2777–2787. https://doi.org/10.1210/en.2009-1375
doi: 10.1210/en.2009-1375
Sands KE, Appel ML, Lilly LS, Schoen FJ, Mudge GH Jr, Cohen RJ (1989) Power spectrum analysis of heart rate variability in human cardiac transplant recipients. Circulation 79:76–82. https://doi.org/10.1161/01.cir.79.1.76
doi: 10.1161/01.cir.79.1.76
Scherlag BJ, Kabell G, Harrison L, Lazzara R (1982) Mechanisms of bradycardia-induced ventricular arrhythmias in myocardial ischemia and infarction. Circulation 65:1429–1434. https://doi.org/10.1161/01.cir.65.7.1429
doi: 10.1161/01.cir.65.7.1429
Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9:671–675. https://doi.org/10.1038/nmeth.2089
doi: 10.1038/nmeth.2089
Shi S, Liang J, Liu T, Yuan X, Ruan B, Sun L, Tang Y, Yang B, Hu D, Huang C (2014) Depression increases sympathetic activity and exacerbates myocardial remodeling after myocardial infarction: evidence from an animal experiment. PLoS ONE 9:e101734. https://doi.org/10.1371/journal.pone.0101734
doi: 10.1371/journal.pone.0101734
Shinoda Y, Tagashira H, Bhuiyan MS, Hasegawa H, Kanai H, Zhang C, Han F, Fukunaga K (2016) Corticosteroids mediate heart failure-induced depression through reduced sigma1-receptor expression. PLoS ONE 11:e0163992. https://doi.org/10.1371/journal.pone.0163992
doi: 10.1371/journal.pone.0163992
Solomon MB, Furay AR, Jones K, Packard AE, Packard BA, Wulsin AC, Herman JP (2012) Deletion of forebrain glucocorticoid receptors impairs neuroendocrine stress responses and induces depression-like behavior in males but not females. Neuroscience 203:135–143. https://doi.org/10.1016/j.neuroscience.2011.12.014
doi: 10.1016/j.neuroscience.2011.12.014
Tao LY, Huang MY, Saroj T, Wang JN, Wu SZ, He F, Huang KY, Xue YJ, Lingwei J, Liao LM, Tang JF, Ji KT (2018) Effects of macrophage migration inhibitory factor on cardiac reperfusion injury in mice with depression induced by constant-darkness. J Affect Disord 229:403–409. https://doi.org/10.1016/j.jad.2017.12.039
doi: 10.1016/j.jad.2017.12.039
Tronche F, Kellendonk C, Kretz O, Gass P, Anlag K, Orban PC, Bock R, Klein R, Schutz G (1999) Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat Genet 23:99–103. https://doi.org/10.1038/12703
doi: 10.1038/12703
Urani A, Chourbaji S, Gass P (2005) Mutant mouse models of depression: candidate genes and current mouse lines. Neurosci Biobehav Rev 29:805–828. https://doi.org/10.1016/j.neubiorev.2005.03.020
doi: 10.1016/j.neubiorev.2005.03.020
van West D, Van Den Eede F, Del-Favero J, Souery D, Norrback KF, Van Duijn C, Sluijs S, Adolfsson R, Mendlewicz J, Deboutte D, Van Broeckhoven C, Claes S (2006) Glucocorticoid receptor gene-based SNP analysis in patients with recurrent major depression. Neuropsychopharmacology 31:620–627. https://doi.org/10.1038/sj.npp.1300898
doi: 10.1038/sj.npp.1300898
Vogt MA (2010) Depression-like behavior of mice with conditional ablation of glucocorticoid signaling: the impact of tamoxifen on the behavioral phenotype. Doctoral dissertation. Combined Faculties for the Natural Sciences and for Mathematics of the Ruperto-Carola University of Heidelberg, Germany
Vogt MA, Inta D, Luoni A, Elkin H, Pfeiffer N, Riva MA, Gass P (2014) Inducible forebrain-specific ablation of the transcription factor Creb during adulthood induces anxiety but no spatial/contextual learning deficits. Front Behav Neurosci 8:407. https://doi.org/10.3389/fnbeh.2014.00407
doi: 10.3389/fnbeh.2014.00407
Wallenborn J, Angermann CE (2016) Depression and heart failure—a twofold hazard?: diagnosis, prognostic relevance and treatment of an underestimated comorbidity. Herz 41:741–754. https://doi.org/10.1007/s00059-016-4483-8
doi: 10.1007/s00059-016-4483-8
Wang Y, Liu X, Zhang D, Chen J, Liu S, Berk M (2013) The effects of apoptosis vulnerability markers on the myocardium in depression after myocardial infarction. BMC Med 11:32. https://doi.org/10.1186/1741-7015-11-32
doi: 10.1186/1741-7015-11-32
Wang Y, Zhang H, Chai F, Liu X, Berk M (2014) The effects of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 during myocardial ischemia/reperfusion in a model of rats with depression. BMC Psychiatry 14:349. https://doi.org/10.1186/s12888-014-0349-x
doi: 10.1186/s12888-014-0349-x
Weinreuter M, Kreusser MM, Beckendorf J, Schreiter FC, Leuschner F, Lehmann LH, Hofmann KP, Rostosky JS, Diemert N, Xu C, Volz HC, Jungmann A, Nickel A, Sticht C, Gretz N, Maack C, Schneider MD, Grone HJ, Muller OJ, Katus HA, Backs J (2014) CaM Kinase II mediates maladaptive post-infarct remodeling and pro-inflammatory chemoattractant signaling but not acute myocardial ischemia/reperfusion injury. EMBO Mol Med 6:1231–1245. https://doi.org/10.15252/emmm.201403848
doi: 10.15252/emmm.201403848
Wong EY, Herbert J (2006) Raised circulating corticosterone inhibits neuronal differentiation of progenitor cells in the adult hippocampus. Neuroscience 137:83–92. https://doi.org/10.1016/j.neuroscience.2005.08.073
doi: 10.1016/j.neuroscience.2005.08.073
Young EA, Haskett RF, Murphy-Weinberg V, Watson SJ, Akil H (1991) Loss of glucocorticoid fast feedback in depression. Arch Gen Psychiatry 48:693–699. https://doi.org/10.1001/archpsyc.1991.01810320017003
doi: 10.1001/archpsyc.1991.01810320017003