genomewide characterization of host-pathogen interactions by ...

Maren Depke
D I S C U S S I O N A N D C O N C L U S I O N S
LIVER GENE EXPRESSION PATTERN IN A MOUSE
PSYCHOLOGICAL STRESS MODEL
BALB/c mice were subjected to combined acoustic and restraint stress for 2 h twice a day
during a period of 4.5 days, which serves as a murine model of chronic psychological stress.
Experiments using the same model had already revealed that mice suffered from an impaired
antibacterial defense and from depression-like behavior (Kiank et al. 2006, 2007a).
The observation of severe loss of total body mass initiated further analysis of metabolic
processes as well as a hepatic gene expression profiling study, which resulted in evidence for the
development of a hypermetabolic syndrome in chronically stressed mice. The results of liver gene
expression profiling and physiological analyses have been published by Depke et al. in 2008 and
2009.
Already a single acute stress exposure caused profound changes in hepatic gene expression.
Genes important for metabolic pathways regulating the carbohydrate turnover showed stressinduced
alterations of mRNA expression in hepatic tissue. An acute stress response is essential
for energy mobilization to “fight or flight” in a potentially harmful situation and to sustain or
reconstitute allostasis (McEwen 2004). Initially, catecholamines activate glycogenolysis,
gluconeogenesis, and accelerate lipolysis that subsequently is assisted by catabolic
glucocorticoid-induced pathways (Bagby et al. 1992, Leibowitz/Wortley 2004, Lundberg 2005,
McGuinness et al. 1999). Acute psychological stress was associated with activation of the stress
axes, and an induction of the expression of gluconeogenic genes and of transporters for
glucogenic amino acids (Pck1, G6pc, Slc37a4, Slc15a4, Slc25a15, Slc38a2, Slc3a1, Sds, Slc6a6, and
Tat).
Despite the observed gene expression changes the metabolic parameters did not change
significantly when stress was restricted to a singular event. Contrarily, when stress was
repeatedly applied, female BALB/c mice developed severe systemic neuroendocrine and
metabolic alterations.
Several researchers found that repeated restraint stress causes a loss of body weight in
rodents, which was mainly mediated by initially increased energy expenditure and reduced food
intake that normalized or even heightened within a few days after starting repeated stress due to
neuroendocrine adaptations (Harris et al. 2002, 2006). Others showed prolonged lowered food
intake during 4.5 days repeated restraint stress due to prolonged neuroendocrine dysregulation
(Ricart-Jané et al. 2002). In the chronic stress model used in this study no changes of total food
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