Pathogenesis of depression- and anxiety-like behavior in an animal model of hypertrophic cardiomyopathy

Dossat Amanda M.; Sanchez-Gonzalez Marcos A.; Koutnik Andrew P.Leitner StefanoRuiz Edda L.Griffin BrittanyRosenberg Jens T.Grant Samuel C.Fincham Francis D.Pinto Jose R.Kabbaj Mohamed

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Pathogenesis of depression- and anxiety-like behavior in an animal model of hypertrophic cardiomyopathy

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Cardiovascular dysfunction is highly comorbid with mood disorders, such as anxiety and depression. However, the mechanisms linking cardiovascular dysfunction with the core behavioral features of mood disorder remain poorly understood. In this study, we usedmice bearing a knock-in sarcomeric mutation, which is exhibited in human hypertrophic cardiomyopathy (HCM), to investigate the influence of HCM over the development of anxiety and depression. We employed behavioral, MRI, and biochemical techniques in young (3-4 mo) and aged adult (7-8 mo) female mice to examine the effects of HCM on the development of anxiety-and depression-like behaviors. We focused on females because in both humans and rodents, they experience a 2-fold increase in mood disorder prevalence vs. males. Our results showed that young and aged HCM mice displayed echocardiographic characteristics of the heart disease condition, yet only aged HCM females displayed anxiety-and depression-like behaviors. Electrocardiographic parameters of sympathetic nervous system activation were increased in aged HCM females vs. controls and correlated with mood disorder-related symptoms. In addition, when compared with controls, aged HCM females exhibited adrenal gland hypertrophy, reduced volume in mood-related brain regions, and reduced hippocampal signaling proteins, such as brain-derived neurotrophic factor and its downstream targets vs. controls. In conclusion, prolonged systemic HCM stress can lead to development of mood disorders, possibly through inducing structural and functional brain changes, and thus, mood disorders in patients with heart disease should not be considered solely a psychologic or situational condition.-Dossat, A. M., Sanchez-Gonzalez, M. A., Koutnik, A. P., Leitner, S., Ruiz, E. L., Griffin, B., Rosenberg, J. T., Grant, S. C., Fincham, F. D., Pinto, J. R. Kabbaj, M. Pathogenesis of depression-and anxiety-like behavior in an animal model of hypertrophic cardiomyopathy.

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《The FASEB Journal》 |2017年第6期|2492-2506|共15页
作者
Dossat Amanda M.; Sanchez-Gonzalez Marcos A.; Koutnik Andrew P.Leitner StefanoRuiz Edda L.Griffin BrittanyRosenberg Jens T.Grant Samuel C.Fincham Francis D.Pinto Jose R.Kabbaj Mohamed;
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作者单位

Florida State Univ, Dept Biomed Sci, Tallahassee, FL 32306 USA;

Florida State Univ, Natl High Magnet Field Lab, Ctr Interdisciplinary Magnet Resonance, Tallahassee;

Florida State Univ, Family Inst, Tallahassee, FL 32306 USALarkin Community Hosp, Div Clin & Translat Res, South Miami, FL USA;

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正文语种英语
中图分类生物化学;
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adrenal gland; heart rate variability; mood disorder; sarcomeric protein; troponin;

Pathogenesis of depression- and anxiety-like behavior in an animal model of hypertrophic cardiomyopathy

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