Project Summary

Qun-Yong Zhou, Ph.D. (Independent Investigator 2007) of the University of California, Irvine, is studying the pathophysiological importance of stress response in the causation of mood and anxiety disorders. While the neural circuit containing corticotropin-releasing factor has been identified as an important regulator of the stress response, signaling mechanisms responsible for the initiation and regulation of stress response are still largely unknown.
The study centers on prokineticins, a pair of newly discovered regulatory peptides that activate two closely related G protein-coupled receptors (GPCRs). The investigator recently discovered that one of these peptides, prokineticin 2 (PK2), may be critical in regulating stress response. This study will test this hypothesis by examining whether PK2-/- mice display reduced stress response, anxiety or depression-like behaviors; and the effect of intracerebroventricular (ICV) infusion of PK2 and PK2-antagonist on the behavioral stress responses. It will also examine the potential role of PK2 in hypothalamus-pituitary-adrenal axis (HPA) activation and whether PK2 neurons in PVN are activated by acute stressors. If PK2’s hypothesized role is validated, the PK2 receptor would be a novel target for treating debilitating mood or chronic anxiety disorders.

Program Area: MOOD DISORDERS

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