PTSD related Behavior, Schaffer Collateral Pathway Organization and Hippocampal Transcript Expression in a Traf-2 and Nck Interacting Kinase (TNIK) -/- Mouse Model
Abstract
Post Traumatic Stress disorder (PTSD) is prevalent in both the military and general population. Symptoms can begin soon after the onset of trauma or at any time throughout the lifetime. Twin studies of those with PTSD reveal genetic susceptibility. This led to interest in identifying genetic risk factors for PTSD. Even large genome studies have not identified and confirmed genes linked to PTSD. To study aspects of PTSD animal models can be used, which allow greater control over variables such as genetic background. Rodent fear conditioning, experimentalinduction of a fearful response to a cue or context, is used to model aspects of PTSD such as intrusive memories. Using fear memory as criteria for selective breeding, a mouse model was created where mice display high [fear susceptible (FS)] or low [fear resilient (FR)] levels of fear based on breeding background. Functional MRI of these mice revealed the hippocampus of FS mice showed higher baseline activity. To investigate differences in neural activity, we performed RNA sequencing from hippocampal tissue of FS and FR mice. A number of transcripts were identified with known neuronal functions that were candidates for further study. One transcript with higher expression in the FS mice was Traf2 and Nck Interacting Kinase (Tnik). Tnik is an emerging psychiatric disease risk factor, and Tnik knockout in mice leads to a deficit in some tests of hippocampal dependent memory. In order to study Tnik loss of function we obtained a Tnik -/- mouse (Pfizer) and elected to study the behavioral effects of Tnik -/-, how Tnik affects hippocampal structure and transcript expression. We hypothesized that Tnik -/- mice will display a deficit in spatial memory, differences in fear memory performance and alterations in the hippocampus that could underlie molecular and behavioral effects relevant to PTSD.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 28, 2017
- Accession Number
- AD1128268
Entities
People
- Steven Dash
Organizations
- Uniformed Services University of the Health Sciences