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Experimental heart failure causes depression-like behavior together with differential regulation of inflammatory and structural genes in the brain.

Frey A, Popp S, Post A, Langer S, Lehmann M, Hofmann U, Sirén AL, Hommers L, Schmitt A, Strekalova T, Ertl G, Lesch KP, Frantz S - Front Behav Neurosci (2014)

Bottom Line: In order to assess depression-like behavior, anhedonia was investigated by repeatedly testing sucrose preference for 8 weeks after coronary artery ligation or sham operation.However, analysis of gene expression by RNA-sequencing in prefrontal cortical, hippocampal, and left ventricular tissue revealed changes in genes related to inflammation and cofactors of neuronal signal transduction in CHF mice, with Nr4a1 being dysregulated both in prefrontal cortex and myocardium after MI.After induction of ischemic CHF, mice exhibited anhedonic behavior, decreased exploratory activity and interest in novelty, and cognitive impairment.

View Article: PubMed Central - PubMed

Affiliation: Medical Clinic and Policlinic I, University Hospital of Würzburg Würzburg, Germany ; Comprehensive Heart Failure Center, University Hospital of Würzburg Würzburg, Germany.

ABSTRACT

Background: Depression and anxiety are common and independent outcome predictors in patients with chronic heart failure (CHF). However, it is unclear whether CHF causes depression. Thus, we investigated whether mice develop anxiety- and depression-like behavior after induction of ischemic CHF by myocardial infarction (MI).

Methods and results: In order to assess depression-like behavior, anhedonia was investigated by repeatedly testing sucrose preference for 8 weeks after coronary artery ligation or sham operation. Mice with large MI and increased left ventricular dimensions on echocardiography (termed CHF mice) showed reduced preference for sucrose, indicating depression-like behavior. 6 weeks after MI, mice were tested for exploratory activity, anxiety-like behavior and cognitive function using the elevated plus maze (EPM), light-dark box (LDB), open field (OF), and object recognition (OR) tests. In the EPM and OF, CHF mice exhibited diminished exploratory behavior and motivation despite similar movement capability. In the OR, CHF mice had reduced preference for novelty and impaired short-term memory. On histology, CHF mice had unaltered overall cerebral morphology. However, analysis of gene expression by RNA-sequencing in prefrontal cortical, hippocampal, and left ventricular tissue revealed changes in genes related to inflammation and cofactors of neuronal signal transduction in CHF mice, with Nr4a1 being dysregulated both in prefrontal cortex and myocardium after MI.

Conclusions: After induction of ischemic CHF, mice exhibited anhedonic behavior, decreased exploratory activity and interest in novelty, and cognitive impairment. Thus, ischemic CHF leads to distinct behavioral changes in mice analogous to symptoms observed in humans with CHF and comorbid depression.

No MeSH data available.


Related in: MedlinePlus

Elevated plus maze. (A) Time spent moving did not differ between the groups, although CHF mice (n = 13) made significantly less vertical rears (B) and spent more time in the center (C) than sham controls (n = 16). However, time spent on the open arms (D) did not differ. (E–H) None of the behavioral measures were correlated with MI size (n = 19). Mean ± s.e.m. *p < 0.05.
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Figure 3: Elevated plus maze. (A) Time spent moving did not differ between the groups, although CHF mice (n = 13) made significantly less vertical rears (B) and spent more time in the center (C) than sham controls (n = 16). However, time spent on the open arms (D) did not differ. (E–H) None of the behavioral measures were correlated with MI size (n = 19). Mean ± s.e.m. *p < 0.05.

Mentions: The time spent moving (Figure 3A), the distance traveled and the relative velocity did not differ between CHF and sham mice. However, CHF mice made significantly less vertical rears (p = 0.033; Figure 3B) and spent more time in the center of the EPM (p = 0.024; Figure 3C) than sham controls. However, there were no significant differences between groups regarding anxiety-related measures, including the number of entries and time spent on the open arms (Figure 3D), as well as defecation/urination (Supplementary Table 2). Pearson's correlation coefficients (Supplementary Table 2) revealed no significant relations between MI size and any of the variables measured in the EPM (Figures 3E–H).


Experimental heart failure causes depression-like behavior together with differential regulation of inflammatory and structural genes in the brain.

Frey A, Popp S, Post A, Langer S, Lehmann M, Hofmann U, Sirén AL, Hommers L, Schmitt A, Strekalova T, Ertl G, Lesch KP, Frantz S - Front Behav Neurosci (2014)

Elevated plus maze. (A) Time spent moving did not differ between the groups, although CHF mice (n = 13) made significantly less vertical rears (B) and spent more time in the center (C) than sham controls (n = 16). However, time spent on the open arms (D) did not differ. (E–H) None of the behavioral measures were correlated with MI size (n = 19). Mean ± s.e.m. *p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215623&req=5

Figure 3: Elevated plus maze. (A) Time spent moving did not differ between the groups, although CHF mice (n = 13) made significantly less vertical rears (B) and spent more time in the center (C) than sham controls (n = 16). However, time spent on the open arms (D) did not differ. (E–H) None of the behavioral measures were correlated with MI size (n = 19). Mean ± s.e.m. *p < 0.05.
Mentions: The time spent moving (Figure 3A), the distance traveled and the relative velocity did not differ between CHF and sham mice. However, CHF mice made significantly less vertical rears (p = 0.033; Figure 3B) and spent more time in the center of the EPM (p = 0.024; Figure 3C) than sham controls. However, there were no significant differences between groups regarding anxiety-related measures, including the number of entries and time spent on the open arms (Figure 3D), as well as defecation/urination (Supplementary Table 2). Pearson's correlation coefficients (Supplementary Table 2) revealed no significant relations between MI size and any of the variables measured in the EPM (Figures 3E–H).

Bottom Line: In order to assess depression-like behavior, anhedonia was investigated by repeatedly testing sucrose preference for 8 weeks after coronary artery ligation or sham operation.However, analysis of gene expression by RNA-sequencing in prefrontal cortical, hippocampal, and left ventricular tissue revealed changes in genes related to inflammation and cofactors of neuronal signal transduction in CHF mice, with Nr4a1 being dysregulated both in prefrontal cortex and myocardium after MI.After induction of ischemic CHF, mice exhibited anhedonic behavior, decreased exploratory activity and interest in novelty, and cognitive impairment.

View Article: PubMed Central - PubMed

Affiliation: Medical Clinic and Policlinic I, University Hospital of Würzburg Würzburg, Germany ; Comprehensive Heart Failure Center, University Hospital of Würzburg Würzburg, Germany.

ABSTRACT

Background: Depression and anxiety are common and independent outcome predictors in patients with chronic heart failure (CHF). However, it is unclear whether CHF causes depression. Thus, we investigated whether mice develop anxiety- and depression-like behavior after induction of ischemic CHF by myocardial infarction (MI).

Methods and results: In order to assess depression-like behavior, anhedonia was investigated by repeatedly testing sucrose preference for 8 weeks after coronary artery ligation or sham operation. Mice with large MI and increased left ventricular dimensions on echocardiography (termed CHF mice) showed reduced preference for sucrose, indicating depression-like behavior. 6 weeks after MI, mice were tested for exploratory activity, anxiety-like behavior and cognitive function using the elevated plus maze (EPM), light-dark box (LDB), open field (OF), and object recognition (OR) tests. In the EPM and OF, CHF mice exhibited diminished exploratory behavior and motivation despite similar movement capability. In the OR, CHF mice had reduced preference for novelty and impaired short-term memory. On histology, CHF mice had unaltered overall cerebral morphology. However, analysis of gene expression by RNA-sequencing in prefrontal cortical, hippocampal, and left ventricular tissue revealed changes in genes related to inflammation and cofactors of neuronal signal transduction in CHF mice, with Nr4a1 being dysregulated both in prefrontal cortex and myocardium after MI.

Conclusions: After induction of ischemic CHF, mice exhibited anhedonic behavior, decreased exploratory activity and interest in novelty, and cognitive impairment. Thus, ischemic CHF leads to distinct behavioral changes in mice analogous to symptoms observed in humans with CHF and comorbid depression.

No MeSH data available.


Related in: MedlinePlus