TY  - JOUR
A1  - Couch, Yvonne
A1  - Trofimov, Alexander
A1  - Markova, Natalyia
A1  - Nikolenko, Vladimir
A1  - Steinbusch, Harry W.
A1  - Chekhonin, Vladimir
A1  - Schroeter, Careen
A1  - Lesch, Klaus-Peter
A1  - Anthony, Daniel C.
A1  - Strekalova, Tatyana
T1  - Low-dose lipopolysaccharide (LPS) inhibits aggressive and augments depressive behaviours in a chronic mild stress model in mice
JF  - Journal of Neuroinflammation
N2  - Background
Aggression, hyperactivity, impulsivity, helplessness and anhedonia are all signs of depressive-like disorders in humans and are often reported to be present in animal models of depression induced by stress or by inflammatory challenges. However, chronic mild stress (CMS) and clinically silent inflammation, during the recovery period after an infection, for example, are often coincident, but comparison of the behavioural and molecular changes that underpin CMS vs a mild inflammatory challenge and impact of the combined challenge is largely unexplored. Here, we examined whether stress-induced behavioural and molecular responses are analogous to lipopolysaccharide (LPS)-induced behavioural and molecular effects and whether their combination is adaptive or maladaptive.

Methods
Changes in measures of hedonic sensitivity, helplessness, aggression, impulsivity and CNS and systemic cytokine and 5-HT-system-related gene expression were investigated in C57BL/6J male mice exposed to chronic stress alone, low-dose LPS alone or a combination of LPS and stress.

Results
When combined with a low dose of LPS, chronic stress resulted in an enhanced depressive-like phenotype but significantly reduced manifestations of aggression and hyperactivity. At the molecular level, LPS was a strong inducer of TNFα, IL-1β and region-specific 5-HT2A mRNA expression in the brain. There was also increased serum corticosterone as well as increased TNFα expression in the liver. Stress did not induce comparable levels of cytokine expression to an LPS challenge, but the combination of stress with LPS reduced the stress-induced changes in 5-HT genes and the LPS-induced elevated IL-1β levels.

Conclusions
It is evident that when administered independently, both stress and LPS challenges induced distinct molecular and behavioural changes. However, at a time when LPS alone does not induce any overt behavioural changes per se, the combination with stress exacerbates depressive and inhibits aggressive behaviours.
KW  - SERT
KW  - Chronic stress
KW  - LPS
KW  - Aggressive behaviour
KW  - S-HT
KW  - Cytokines
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165676
VL  - 13
IS  - 108
ER  - 
TY  - JOUR
A1  - Veniaminova, Ekaterina
A1  - Cespuglio, Raymond
A1  - Cheung, Chi Wai
A1  - Umriukhin, Alexei
A1  - Markova, Nataliia
A1  - Shevtsova, Elena
A1  - Lesch, Klaus-Peter
A1  - Anthony, Daniel C.
A1  - Strekalova, Tatyana
T1  - Autism-like behaviours and memory deficits result from a Western Diet in mice
JF  - Neural Plasticity
N2  - Nonalcoholic fatty liver disease, induced by a Western diet (WD), evokes central and peripheral inflammation that is accompanied by altered emotionality. These changes can be associated with abnormalities in social behaviour, hippocampus-dependent cognitive functions, and metabolism. Female C57BL/6J mice were fed with a regular chow or with a WD containing 0.2% of cholesterol and 21% of saturated fat for three weeks. WD-treated mice exhibited increased social avoidance, crawl-over and digging behaviours, decreased body-body contacts, and hyperlocomotion. The WD-fed group also displayed deficits in hippocampal-dependent performance such as contextual memory in a fear conditioning and pellet displacement paradigms. A reduction in glucose tolerance and elevated levels of serum cholesterol and leptin were also associated with the WD. The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1a) mRNA, a marker of mitochondrial activity, was decreased in the prefrontal cortex, hippocampus, hypothalamus, and dorsal raphe, suggesting suppressed brain mitochondrial functions, but not in the liver. This is the first report to show that a WD can profoundly suppress social interactions and induce dominant-like behaviours in naïve adult mice. The spectrum of behaviours that were found to be induced are reminiscent of symptoms associated with autism, and, if paralleled in humans, suggest that a WD might exacerbate autism spectrum disorder.
KW  - diet
KW  - autism-like behavior
KW  - mice
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158211
ER  -