The corticotropin-releasing fator (CRF) and the central autonomic system

• Grant number: 10/09877-4
• Support Opportunities: Scholarships abroad - Research
• Start date: February 01, 2011
• End date: July 31, 2011
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Jackson Cioni Bittencourt
• Grantee: Jackson Cioni Bittencourt
• Host Investigator: Paul Emil Sawchenko
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Salk Institute For Biological Studies, United States

Abstract

Though best known for its obligate role in stress-induced activation of the endocrine (pituitary-adrenal) stress response, corticotropin-releasing factor (CRF) is widely expressed in the central nervous system (CNS) and can act centrally to provoke stress-like autonomic and behavioral responses. This has fostered the hypothesis that CRF serves not only to effect, but to integrate, multiple modes of stress adaptation, a proposal that continues to frame much contemporary work in stress neurobiology. Work led by this Laboratory has expanded the known universe of mammalian CRF-related signaling molecules to include three additional ligands, urocortins 1-3,two principal membrane-bound receptors (CRFRs), at least one soluble receptor variant and a distinct binding protein (CRF-BP). Even with this, there remain fundamental questions as how individual components of the central CRF system are organized to sculp individual stress responses and interact to achieve successful adaptation at the organismal level. These include the fact that important sites of CRF-related peptide action in eliciting stress responses are alcking or imporverished in ligand-containing inputs, CRFR expression or both. The first goal of this project is to resolve key manifestations of this "mismatch" problem, the second one is to clarify which mechanisms are subserving the integrative role ascribed to CRF signaling in stress adaptation. (AU)