To survive in changing environment the organisms have developed mechanisms, which allow them to response to these changes. The stress reaction, a key mechanism in maintaining homeostasis, activates complex system of responses to reestablish homeostasis. Any intervention acting against homeostasis can be called a stressor. Stress reaction per se is physiological phenomenon. However, long lasting stress, extremely strong stress stimulus or inaccurate set up of stress can lead to disturbances of homeostasis, which can be manifested by pathologies such as posttraumatic stress disorder, metabolic syndrome or depression. Therefore it is important to study mechanism of stress response control. One of the basic reactions to stress is activation of the HPA (hypothalamus-pituitary-adrenal) axis.
The HPA axis regulation is mediated by direct feedback loops of end products of HPA axis and by the neuron of the hypothalamic paraventricular nucleus, which are interconnected (both directly and indirectly) with other brain areas mainly involved in processing of signals from periphery, fear and memory.
The aim of this project is to assess changes in mRNA expression of genes encoding proteins involved in stress response, particularly 11HSD1 (see box below), in principal components of HPA axis and in brain areas involved in HPA axis regulation. Specifically we focus our interest on prefrontal cortex, amygdala, hippocampus and the hypothalamic paraventricular nucleus. These distinct brain areas are identified and harvested from cryosections using laser microdissection method and expression profiles of the genes are obtained by qRT-PCR.
To elicit stress in rats, the psychosocial stress paradigm is used as this stress model is similar to stress affecting the majority of human population.
|The enzyme 11-HSD1 (11β hydroxysteroid dehydrogenase type 1) converts inactive-keto metabolites of glucocorticoid hormones (cortisone in man, 11‑dehydrocorticosterone in rat and mice) to biologically active glucocorticoids (cortisol in man, corticosterone in rodents). This enzyme is expressed in numerous brain areas including cerebral cortex, hippocampus, hypothalamus and cerebellum. By local amplification of glucocorticoid signal in structures involved in HPA axis regulation, this enzyme can play a role in modulation the activity of feedback loops.|
Ergang P, Vodička M, Soták M, Klusoňová P, Behuliak M, Řeháková L, Zach P, Pácha J. Differential impact of stress on hypothalamic-pituitary-adrenal axis: gene expression changes in Lewis and Fisher rats. Psychoneuroendocrinology 53:49-59, 2015.
Vodička M, Ergang P, Mikulecká A, Řeháková L, Klusoňová P, Makal J, Soták M, Musílková J, Zach P, Pácha J. Regulation of 11β-hydroxysteroid dehydrogenase type 1 and 7α-hydroxylase CYP7B1 during social stress. PLoS One 9:e89421. 2014