Chronic stress is a predominant risk factor for mood disorders, anxiety and epilepsy. Endogenous systems regulating the stress response are interesting targets in the quest for novel treatments for stress-related disorders. Here we focus on neuromedin U (NMU) a regulator of stress responses that has been shown to exert top-down control over the hypothalamus-pituitary-adrenal-axis (HPA-axis), a main part of the neuroendocrine system that controls reactions to stress. Whereas NMU has received little attention in research towards stress-related disorders we hypothesize that it might be a master regulator of the HPA-axis and that reducing the central activity of NMU might be an interesting and innovative way to diminish the symptoms of anxiety, major depression and epilepsy. We will perform several experiments in mice that will lead to a better insight into the role of NMU in the chronically stressed brain as compared to a healthy brain. To investigate our hypothesis, we will perform an in-depth study of the neuroanatomy of the NMU system. We will quantify biomarkers for stress and study stress-related behaviours in well-validated paradigms following NMU administration. We will also use state-of-the-art chemogenetic approaches to investigate whether specific activation or silencing of NMU-producing neurons will mimic or attenuate chronic stress conditions and affect the outcome of the mice in tests for anxiety, depression and epilepsy.
|Effective start/end date||1/01/16 → 31/12/19|
Flemish discipline codes
- Pharmacology not elsewhere classified