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Research Article

Perifornical Urocortin-3 mediates the link between stress-induced anxiety and energy homeostasis

Yael Kuperman, Orna Issler, Limor Regev, Ifat Musseri, Inbal Navon, Adi Neufeld-Cohen, Shosh Gil, and Alon Chen
PNAS first published April 19, 2010; https://doi.org/10.1073/pnas.1003969107
Yael Kuperman
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Orna Issler
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Limor Regev
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Ifat Musseri
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Inbal Navon
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Adi Neufeld-Cohen
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Shosh Gil
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Alon Chen
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  • For correspondence: alon.chen@weizmann.ac.il
  1. Communicated by Wylie W. Vale, The Salk Institute for Biological Studies, La Jolla, CA, March 24, 2010 (received for review November 3, 2009)

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Abstract

In response to physiological or psychological challenges, the brain activates behavioral and neuroendocrine systems linked to both metabolic and emotional outputs designed to adapt to the demand. However, dysregulation of integration of these physiological responses to challenge can have severe psychological and physiological consequences, and inappropriate regulation, disproportional intensity, or chronic or irreversible activation of the stress response is linked to the etiology and pathophysiology of mood and metabolic disorders. Using a transgenic mouse model and lentiviral approach, we demonstrate the involvement of the hypothalamic neuropeptide Urocortin-3, a specific ligand for the type-2 corticotropin-releasing factor receptor, in modulating septal and hypothalamic nuclei responsible for anxiety-like behaviors and metabolic functions, respectively. These results position Urocortin-3 as a neuromodulator linking stress-induced anxiety and energy homeostasis and pave the way toward better understanding of the mechanisms that mediate the reciprocal relationships between stress, mood and metabolic disorders.

  • metabolic disorders
  • mood disorders
  • corticotropin-releasing factor (CRF)
  • CRF receptor type 2
  • stress response

Footnotes

  • 1To whom correspondence should be addressed. E-mail: alon.chen{at}weizmann.ac.il.
  • Author contributions: Y.K. and A.C. designed research; Y.K., O.I., L.R., I.M., I.N., A.N.-C., S.G., and A.C. performed research; Y.K., O.I., and A.C. analyzed data; and Y.K. and A.C. wrote the paper.

  • The authors declare no conflict of interest.

  • This article contains supporting information online at www.pnas.org/cgi/content/full/1003969107/DCSupplemental.

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Perifornical Urocortin-3 mediates the link between stress-induced anxiety and energy homeostasis
Yael Kuperman, Orna Issler, Limor Regev, Ifat Musseri, Inbal Navon, Adi Neufeld-Cohen, Shosh Gil, Alon Chen
Proceedings of the National Academy of Sciences Apr 2010, 201003969; DOI: 10.1073/pnas.1003969107

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Perifornical Urocortin-3 mediates the link between stress-induced anxiety and energy homeostasis
Yael Kuperman, Orna Issler, Limor Regev, Ifat Musseri, Inbal Navon, Adi Neufeld-Cohen, Shosh Gil, Alon Chen
Proceedings of the National Academy of Sciences Apr 2010, 201003969; DOI: 10.1073/pnas.1003969107
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Proceedings of the National Academy of Sciences: 118 (3)
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