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Decreased Brain Sigma-1 Receptor Contributes to the Relationship between Heart Failure and Depression.
MedLine Citation:
PMID:  21960687     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Aims Depression often coexists with cardiovascular disease, such as hypertension and heart failure, in which sympathetic hyperactivation is critically involved. Reduction of 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 percent 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 behavior, 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.Conclusions These results indicate that decreased brain S1R contributes to the relationship between heart failure and depression in a mouse model of pressure-overload.
Authors:
Koji Ito; Yoshitaka Hirooka; Ryuichi Matsukawa; Masatsugu Nakano; Kenji Sunagawa
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-29
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
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