The neurobiology of stress
The neuroendocrine stress response is regulated by the hypothalamo-pituitary-adrenal system. The corticotropin-releasing hormone (CRH)-secreting neurons are located in the paraventricular nucleus of the hypothalamus which integrate stress information from other areas of the central nervous system and are able to trigger the appropriate hormonal stress response. However, during stress, autonomic functions, metabolism, immune processes and behaviour are also altered. The aim of our research is to elucidate the regulatory mechanisms and neuronal networks that coordinate elements of the stress response and to reveal the role of neurons expressing CRH in stress integration outside of the hypothalamus.
In the past few years:
· Using a corticotropin-releasing hormone (CRH) reporting mice, the distribution of CRH neurons has been mapped throughout the brain and their recruitment under various physiologic and psychogenic challenges has been revealed. This study provides a full inventory of stress-responsive CRH neurons in the mouse brain and provides a background for future studies on extrahypothalamic stress circuits. https://pubmed.ncbi.nlm.nih.gov/37511494/
· We highlighted that the number and distribution of putative CRH neurons in the brain of male and female, CRH-Ires-Cre:Ai9 mice, are similar. Sex differences in CRH mRNA expression occur later in development under the influence of sex steroids. However, the recruitment of CRH neurons in response to predator odor stress is highly sex-dependent. https://pubmed.ncbi.nlm.nih.gov/39596070/
· We have characterized and compared metabolic and behavioral changes induced by acute, repeated and chronic stress in mice.
https://pubmed.ncbi.nlm.nih.gov/35880047/
· During fasting, the hypothalamo-pituitary-adrenocortical axis (HPA) and metabolism is uncoupled. CRH expression is upregulated even in face of increased CORT secretion and the energy expenditure suppressed. Eventually, fasting results in anti-inflammatory microglia milieu in the hypothalamus, which is dependent on adrenal glucocorticoids.
https://pubmed.ncbi.nlm.nih.gov/40602552/
· Two novel pathways (thalamic and brainstem) have been revealed, which may contribute to stress-related sleep anomalies.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11750107/ and https://pubmed.ncbi.nlm.nih.gov/36564184/.