Urocortin expression in the Edinger-Westphal nucleus is down-regulated in transgenic mice over-expressing neuronal corticotropin-releasing factor

T. Kozicz, A. Korosi, C. Korsman, D. Tilburg-Ouwens, L. Groenink, J. Veening, J. Van Der Gugten, E. Roubos, B. Olivier

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

In recent years a large body of evidence has emerged linking chronic stress with increased vulnerability for depression and anxiety disorders. As corticotropin-releasing factor (CRF) is hypersecreted under these psychological conditions, we used our CRF-overexpressing (CRF-OE) mouse line to study underlying brain mechanisms possibly causing these disorders. Urocortin (Ucn), a recently discovered member of the CRF peptide family may play a role in the pathophysiology of stress-induced disorders. Stressors recruit Ucn-immunoreactive neurons in the Edinger-Westphal nucleus (E-WN), which is the major site of Ucn expression. Furthermore, E-WN Ucn mRNA levels are upregulated in CRF-deficient mice. Based on these findings, we hypothesized the down-regulation of E-WN Ucn in CRF-OE mice and consequently, altered responsiveness to stressful stimuli. Our results support this hypothesis as we found weaker immunohistochemical labeling with anti-Ucn and a six times weaker Ucn mRNA signal in E-WN in CRF-OE mice. Moreover, E-WN Ucn-expressing neurons mounted a response to acute challenge in CRF-OE mice too. From these results it is concluded that the CRF and E-WN Ucn neuronal systems work in concert in response to acute challenges, but are inversely regulated in their activities during chronic hyperactivity of the hypothalamo-pituitary-adrenal axis.

Original languageEnglish (US)
Pages (from-to)589-594
Number of pages6
JournalNeuroscience
Volume123
Issue number3
DOIs
StatePublished - Jan 1 2004

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Keywords

  • Acute ether stress
  • In situ hybridization
  • Quantitative Fos immunohistochemistry

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kozicz, T., Korosi, A., Korsman, C., Tilburg-Ouwens, D., Groenink, L., Veening, J., Van Der Gugten, J., Roubos, E., & Olivier, B. (2004). Urocortin expression in the Edinger-Westphal nucleus is down-regulated in transgenic mice over-expressing neuronal corticotropin-releasing factor. Neuroscience, 123(3), 589-594. https://doi.org/10.1016/j.neuroscience.2003.10.042