Stress/Glucocorticoid Mechanisms in Parkinsonian Pathologies
Abstract
A major goal during this research period involved extensive breeding and genotyping of the DAT-Cre line and the GRflox line to generate the DAT-Cre:GRflox (GR knockout in dopaminergic neurons) rat line. We have established a large breeding colony and are generating large cohorts to continue our studies on baseline behavioral assessments, CVS protocols and aSyn injections. Regarding baseline assessments, we performed analysis of locomotor and cognitive behavior in cohorts of male and female DAT-Cre-directed GR deletion (DAT-Cre+/-:GRflox) and Cre-negative controls (DAT-Cre-/-:GRflox). Targeted deletion of GR in dopamine neurons reduced locomotor activity in females and impairs initial recall of conditioned fear in males. These results suggest that GR acts in dopamine neurons to regulate locomotor and cognitive responses to stress in a sex-specific manner. Our data implicate GR-dopamine interactions in mediating behaviors relevant to motor and non-motor symptoms in our combined stress/PD model. We also implemented a sophisticated cognitive behavioral test (5-choice serial reaction time task; 5CSRTT). In baseline experiments, we found that rats exposed to single-prolonged stress exhibit impulsive behavior, which is also characteristic of individuals with PD.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1199720
Entities
People
- Kim B. Seroogy
Organizations
- University of Cincinnati