11823
2014
eng
376
8
article
1
2015-08-20
--
--
Experimental heart failure causes depression-like behavior together with differential regulation of inflammatory and structural genes in the brain
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.
Frontiers in Behavioral Neuroscience
10.3389/fnbeh.2014.00376
1662-5153
urn:nbn:de:bvb:20-opus-118234
Frontiers in Behavioral Neuroscience 8:376. doi:10.3389/fnbeh.2014.00376
Anna Frey
Sandy Popp
Antonia Post
Simon Langer
Marc Lehmann
Ulrich Hofmann
Anna-Leena Siren
Leif Hommers
Angelika Schmitt
Tatyana Strekalova
Georg Ertl
Klaus-Peter Lesch
Stefan Frantz
eng
uncontrolled
chronic heart failure
eng
uncontrolled
myocardial infarction
eng
uncontrolled
anxiety
eng
uncontrolled
depression
eng
uncontrolled
mice
Krankheiten
open_access
Neurochirurgische Klinik und Poliklinik
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Medizinische Klinik und Poliklinik I
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11823/014_Frey_FRONTIERS_IN_BEHAVIORAL_NEUROSCIENCE.pdf
24273
2021
eng
14
10
article
1
--
2021-07-14
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5-HTT Deficiency in Male Mice Affects Healing and Behavior after Myocardial Infarction
Anxiety disorders and depression are common comorbidities in cardiac patients. Mice lacking the serotonin transporter (5-HTT) exhibit increased anxiety-like behavior. However, the role of 5-HTT deficiency on cardiac aging, and on healing and remodeling processes after myocardial infarction (MI), remains unclear. Cardiological evaluation of experimentally naïve male mice revealed a mild cardiac dysfunction in ≥4-month-old 5-HTT knockout (−/−) animals. Following induction of chronic cardiac dysfunction (CCD) by MI vs. sham operation 5-HTT−/− mice with infarct sizes >30% experienced 100% mortality, while 50% of 5-HTT+/− and 37% of 5-HTT+/+ animals with large MI survived the 8-week observation period. Surviving (sham and MI < 30%) 5-HTT−/− mutants displayed reduced exploratory activity and increased anxiety-like behavior in different approach-avoidance tasks. However, CCD failed to provoke a depressive-like behavioral response in either 5-Htt genotype. Mechanistic analyses were performed on mice 3 days post-MI. Electrocardiography, histology and FACS of inflammatory cells revealed no abnormalities. However, gene expression of inflammation-related cytokines (TGF-β, TNF-α, IL-6) and MMP-2, a protein involved in the breakdown of extracellular matrix, was significantly increased in 5-HTT−/− mice after MI. This study shows that 5-HTT deficiency leads to age-dependent cardiac dysfunction and disrupted early healing after MI probably due to alterations of inflammatory processes in mice.
Journal of Clinical Medicine
2077-0383
10.3390/jcm10143104
urn:nbn:de:bvb:20-opus-242739
2021-08-01T16:39:17+00:00
sword
swordwue
attachment; filename=deposit.zip
c26d74e7ca9ddb8ea8bed92f5c7da38f
Journal of Clinical Medicine 2021, 10(14), 3104; https://doi.org/10.3390/jcm10143104
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Sandy Popp
Angelika Schmitt-Böhrer
Simon Langer
Ulrich Hofmann
Leif Hommers
Kai Schuh
Stefan Frantz
Klaus-Peter Lesch
Anna Frey
eng
uncontrolled
chronic heart failure
eng
uncontrolled
myocardial infarction
eng
uncontrolled
serotonin transporter deficient mice
eng
uncontrolled
anxiety
eng
uncontrolled
depression
eng
uncontrolled
behavior
eng
uncontrolled
inflammation
Medizin und Gesundheit
open_access
Physiologisches Institut
Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Medizinische Klinik und Poliklinik I
Import
Förderzeitraum 2021
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/24273/jcm-10-03104-v2.pdf