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Perifornical Urocortin-3 mediates the link between stress-induced anxiety and energy homeostasis
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Communicated by Wylie W. Vale, The Salk Institute for Biological Studies, La Jolla, CA, March 24, 2010 (received for review November 3, 2009)

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.
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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.
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The authors declare no conflict of interest.
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This article contains supporting information online at www.pnas.org/cgi/content/full/1003969107/DCSupplemental.