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Stress, a matter of balance


Dournes,  Carine
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Dournes, C. (2021). Stress, a matter of balance. PhD Thesis, Ludwig-Maximilians-Universität München, München.

Cite as: https://hdl.handle.net/21.11116/0000-000B-503B-9
Modern society is a dynamic plot pervaded by cultural, social, emotional, and biological experiences, some of which ultimately endanger our lifestyle and affect our physiology and behaviour. For health and survival, adequate regulatory control of the HPA stress axis is required. Over the years, chronic stress has been frequently implicated in altered brain function. Current evidence shows that the habituation of HPA axis response is more complex than previously thought. The adaptive reduction of repeated stress-induced responses seems to involve complex crosstalk between negative feedback mechanisms induced by the release of GCs under repeated stress, response habituation processes produced by repetitive exposure to the stress stimulus, and likely more complex learning and memory encoding information regarding previous stressful events. We directed our research towards two major problems that currently impede advances in modeling HPA habituation in mice and mechanisms leading to it. By doing so, we contribute to a better understanding of normal behavior and mechanisms. Here, we show that glucocorticoid receptors in the hypothalamic paraventricular nucleus in CRF neurons are essential for HPA axis habituation. When re-exposed to the same stressor, glucocorticoid receptors led to essential cellular modulation and dampened HPA axis activation by increasing inhibitory tone onto CRF neurons. The current research study provides a new set of data that confidently positions the GR-CRF system as a crucial player in the executive function following repeated stress exposure, thus offering a molecular mechanism through which this effect occurs. Hence, it shows a possible pharmacological target that could support the production of active measures to mitigate the deleterious effects of repeated stress exposure.