Does midbrain urocortin 1 matter? A 15-year journey from stress (mal)adaptation to energy metabolism

Abstract

This review summarizes some of the milestones of the research on the biological functions(s) of midbrain urocortin 1 (Ucn1) since its discovery 15 years ago. Detailed characterization of Ucn1 in the midbrain revealed its overall significance in food intake and regulation of homeostatic equilibrium and mood under stress. In addition, we have recently found a conspicuous alteration in midbrain Ucn1 levels in brains of depressed suicide victims. Furthermore, from the results from the genetically modified animals, a picture is emerging where corticotrophin-releasing factor promotes the initial reactions to stress, whereas Ucn1 seems to be crucial for management of the later adaptive phase. In the case of imbalance in action of these principle stress mediators, vulnerability to stress-related brain diseases is enhanced.

Keywords::

• Urocortin 1
• Edinger–Westphal central projecting neurons
• stress
• depression
• energy metabolism
• sex difference

Acknowledgements

We apologize to those colleagues whose work could not be cited here owing to space limitations. L.S. and X.L are on a 4-year PhD program sponsored by MSD, Oss, The Netherlands (L.S.), and by Radboud University Nijmegen, Faculty of Science, Mathematics and Informatics (X.L.). This work was also supported by the Netherlands Organization for Scientific Research Grant 864.05.008 (to TK).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.