TY  - JOUR
A1  - Frey, Anna
A1  - Popp, Sandy
A1  - Post, Antonia
A1  - Langer, Simon
A1  - Lehmann, Marc
A1  - Hofmann, Ulrich
A1  - Siren, Anna-Leena
A1  - Hommers, Leif
A1  - Schmitt, Angelika
A1  - Strekalova, Tatyana
A1  - Ertl, Georg
A1  - Lesch, Klaus-Peter
A1  - Frantz, Stefan
T1  - Experimental heart failure causes depression-like behavior together with differential regulation of inflammatory and structural genes in the brain
JF  - Frontiers in Behavioral Neuroscience
N2  - 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.
KW  - chronic heart failure
KW  - myocardial infarction
KW  - anxiety
KW  - depression
KW  - mice
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-118234
SN  - 1662-5153
VL  - 8
ER  - 
TY  - JOUR
A1  - Kloke, Vanessa
A1  - Schreiber, Rebecca S.
A1  - Bodden, Carina
A1  - Möllers, Julian
A1  - Ruhmann, Hanna
A1  - Kaiser, Sylvia
A1  - Lesch, Klaus-Peter
A1  - Sachser, Norbert
A1  - Lewejohann, Lars
T1  - Hope for the Best or Prepare for the Worst? Towards a Spatial Cognitive Bias Test for Mice
JF  - PLOS ONE
N2  - Cognitive bias, the altered information processing resulting from the background emotional state of an individual, has been suggested as a promising new indicator of animal emotion. Comparable to anxious or depressed humans, animals in a putatively negative emotional state are more likely to judge an ambiguous stimulus as if it predicts a negative event, than those in positive states. The present study aimed to establish a cognitive bias test for mice based on a spatial judgment task and to apply it in a pilot study to serotonin transporter (5-HTT) knockout mice, a well-established mouse model for the study of anxiety- and depression-related behavior. In a first step, we validated that our setup can assess different expectations about the outcome of an ambiguous stimulus: mice having learned to expect something positive within a maze differed significantly in their behavior towards an unfamiliar location than animals having learned to expect something negative. In a second step, the use of spatial location as a discriminatory stimulus was confirmed by showing that mice interpret an ambiguous stimulus depending on its spatial location, with a position exactly midway between a positive and a negative reference point provoking the highest level of ambiguity. Finally, the anxiety- and depression-like phenotype of the 5-HTT knockout mouse model manifested - comparable to human conditions - in a trend for a negatively distorted interpretation of ambiguous information, albeit this effect was not statistically significant. The results suggest that the present cognitive bias test provides a useful basis to study the emotional state in mice, which may not only increase the translational value of animal models in the study of human affective disorders, but which is also a central objective of animal welfare research.
KW  - emotional information
KW  - serotonin transporter gene
KW  - attentional bias
KW  - laboratory environment
KW  - animal behavior
KW  - promoter region
KW  - deficient mice
KW  - affective state
KW  - knockout mice
KW  - judgement bias
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115569
VL  - 9
IS  - 8
ER  -