Date of Award
2006
Degree Type
Thesis
Degree Name
Master of Science
Program
Neuroscience
Second Advisor
Dr. Rushlow
Third Advisor
Dr. R. Jane Rylett
Abstract
Chronic hyperactivity of the dopaminergic system is associated with certain symptoms of schizophrenia. Our laboratory has developed a rat model of schizophrenia that involves Iesioning the developing prefrontal cortex. Lesioned animals display behaviours indicative of chronic mesolimbic dopaminergic hyperactivity consistent with other animal models of schizophrenia. Little is known concerning the molecular consequences associated with hyperdopaminergic activity in schizophrenia. The current study investigated the effects of the serine/threonine kinase Cdk5 on the phosphorylation status of DARPP- 32, a critical molecule involved in dopamine receptor-mediated signal transduction, in the nucleus accumbens in our animal model using western blotting and immunohistochemistry. Lesioned animals showed increased levels of ΔFosB, Egr-1, Cdk5, p35, p25, active Calpain-2 and phosphorylated DARPP-32 at Threonine 75 in the nucleus accumbens. The results suggest that endogenous and chronic mesolimbic dopaminergic hyperactivity may increase Cdk5 activity which can alter DARPP-32 signalling and via a feedback mechanism may interfere with dopamine receptor-mediated effects in our animal model of schizophrenia.
Recommended Citation
Cantruo, Robert T., "CDK5 EXPRESSION IN THE NUCLEUS ACCUMBENS IN AN ANIMAL MODEL OF SCHIZOPHRENIA THAT DISPLAYS CHRONIC DOPAMINERGIC HYPERACTIVITY" (2006). Digitized Theses. 4881.
https://ir.lib.uwo.ca/digitizedtheses/4881