Decreased brain sigma-1 receptor contributes to the relationship between heart failure and depression

Koji Ito, Yoshitaka Hirooka, Ryuichi Matsukawa, Masatsugu Nakano, Kenji Sunagawa

    Research output: Contribution to journalArticlepeer-review

    41 Citations (Scopus)


    Aims Depression often coexists with cardiovascular disease, such as hypertension and heart failure, in which sympathetic hyperactivation is critically involved. Reduction in the brain sigma-1 receptor (S1R) functions in depression pathogenesis via neuronal activity modulation. We hypothesized that reduced brain S1R exacerbates heart failure, especially with pressure overload via sympathetic hyperactivation and worsening depression. Methods and Results Male Institute of Cancer Research mice were treated with aortic banding and, 4 weeks thereafter, fed a high-salt diet for an additional 4 weeks to accelerate cardiac dysfunction (AB-H). Compared with sham-operated controls (Sham), AB-H showed augmented sympathetic activity, decreased per cent fractional shortening, increased left ventricular dimensions, and significantly lower brain S1R expression. Intracerebroventricular (ICV) infusion of S1R agonist PRE084 increased brain S1R expression, lowered sympathetic activity, and improved cardiac function in AB-H. ICV infusion of S1R antagonist BD1063 increased sympathetic activity and decreased cardiac function in Sham. Tail suspension test was used to evaluate the index of depression-like behaviour, with immobility time and strain amplitude recorded as markers of struggle activity using a force transducer. Immobility time increased and strain amplitude decreased in AB-H compared with Sham, and these changes were attenuated by ICV infusion of PRE084. Conclusion These results indicate that decreased brain S1R contributes to the relationship between heart failure and depression in a mouse model of pressure overload.

    Original languageEnglish
    Pages (from-to)33-40
    Number of pages8
    JournalCardiovascular research
    Issue number1
    Publication statusPublished - Jan 1 2012

    All Science Journal Classification (ASJC) codes

    • Physiology
    • Cardiology and Cardiovascular Medicine
    • Physiology (medical)


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