Understanding the biological mechanisms and biomarkers of psychiatric disease is critical for understanding, assessing risk, and designing treatments of disorders such as post traumatic stress disorder (PTSD). In this regard, it was recently reported that the neuropeptide PACAP and its plasma membrane receptor PAC1 are linked to PTSD at both genetic and epigenetic levels. These findings complement a considerable set of prior evidence implicating PACAP/PAC1 signaling in stress and fear circuitries. Experiments in the proposal will use gene targeting approaches to dissect at the cellular, molecular, and behavioral levels, the involvement of PACAP-PAC1 signaling in the circuitry regulating fear in mice. The results are hoped to lay a mechanistic foundation for the development of an entirely new set of therapeutic targets for PTSD based on PAC1 signaling and downstream actions, and may also lead to the discovery of novel and robust biomarkers associated with this pathway.

Public Health Relevance

Understanding the biological mechanisms and biomarkers of psychiatric disease is critical for understanding, assessing risk, and designing treatments of disorders such as post traumatic stress disorder (PTSD). New evidence from a large population of patients has linked a neuropeptide called PACAP to PTSD, affording a possible new drug target to prevent or treat this affliction. Experiments in the proposal will use gene targeting approaches to dissect at the cellular, molecular, and behavioral levels the involvement of PACAP in regulating fear in mice, laying a foundation for the development of an entirely new set of therapeutic targets for PTSD, and to the potential discovery of novel and robust biomarkers associated with this disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21MH098506-01A1
Application #
8463349
Study Section
Special Emphasis Panel (ZRG1-MDCN-P (57))
Program Officer
Desmond, Nancy L
Project Start
2012-12-20
Project End
2014-11-30
Budget Start
2012-12-20
Budget End
2013-11-30
Support Year
1
Fiscal Year
2013
Total Cost
$231,000
Indirect Cost
$81,000
Name
University of California Los Angeles
Department
None
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095