Accession Number:

ADA564271

Title:

Molecular Mechanisms Underlying Individual Differences in Response to Stress in a Previously Validated Animal Model of PTSD

Descriptive Note:

Final rept. 1 Sep 2008-31 Mar 2012

Corporate Author:

BRONX VETERANS MEDICAL RESEARCH FOUNDATION INC (VETERANS AFFAIRS) NEW YORK

Personal Author(s):

• Yehuda, Rachel
• Buxbaum, Joseph

Report Date:

2012-04-01

Pagination or Media Count:

7.0

Abstract:

It is unclear why some individuals develop PTSD while others do not. Pre-existing biological differences among individuals may predispose some and not others to develop PTSD. We are seeking to identify such biological differences using an existing rat model for PTSD where exposure to a predator stress scent PSS results in extreme behavioral responses for 25 of animals EBR thought to be analogous to PTSD, while 25 of the animals show minimal behavioral responses MBR. Our objectives for Experiment 1 were to identify genes showing altered mRNA expression in blood and brain areas implicated in PTSD that relate to individual differences in fear reactivity. Our goal in Experiment 2 was to examine the prophylactic effects of exogenous glucocorticoids on the behavioral and gene expression effects of stress exposure. We have completed the behavioral work for Exp.1 and Exp.2 and successfully produced rats with the behavioral phenotypes that were required for our gene expression aims. Gene expression profiling of Exp.1 has been completed on all brain samples and on a portion of the blood. Among others, differential expression of genes e.g. FKBP5 regulated by the glucocorticoid-receptor GR underlies the behavioral differences. The small overlap in gene expression between different tissue and gender demonstrated the existence of distinct tissue specific susceptibility pathways in males and females. Gene expression profiling of the samples of Exp.2 is ongoing.

Descriptors:

• *POST TRAUMATIC STRESS DISORDER
• ADRENAL CORTEX HORMONES
• ANATOMICAL MODELS
• BEHAVIOR
• EXPOSURE(PHYSIOLOGY)
• GENES
• GENETIC TISSUE IDENTIFICATION
• MOLECULAR PROPERTIES
• PREVENTIVE MEDICINE
• RESPONSE(BIOLOGY)

Subject Categories:

• Psychology
• Medicine and Medical Research
• Stress Physiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE