Dissertation
D3 receptor agonism attenuates deficits observed in rodents with 6-OHDA-induced medial forebrain bundle lesions
Doctor of Philosophy (Ph.D.), Drexel University
Sep 2018
DOI:
https://doi.org/10.17918/806t-sc30
Abstract
Parkinson's Disease (PD) is a neurodegenerative disorder associated with the progressive loss of dopaminergic neurons in the substantia nigra. This pathology impairs the dopaminergic nigrostriatal pathway, thereby reducing dopamine (DA) input to the striatum and eliciting motor deficits. In addition to these motor deficits, PD patients are often afflicted by non-motor symptoms such as mild cognitive impairment (PD-MCI). PD-MCI patients display deficits in executive function and pathological alterations within the prefrontal cortex (PFC). Specifically, decreases in DA D3 receptor (D3R) expression in the PFC correlate with decreases in cognitive performance. The role of D3Rs in PD are well-established in motor impairments, but their effect on cognitive tasks is yet to be investigated. Additionally, pharmacological agents that target the D3R concurrently demonstrate affinity for other DA receptors. Our lab has developed a selective D3R agonist called SK609 to specifically examine D3R agonism in a hemiparkinson rodent model. We utilized behavioral assays that assess sustained attention and cognitive flexibility, two PFC-mediated tasks compromised in PD-MCI. We found that SK609 dose dependently ameliorated cognitive deficits in lesioned rodents. Taken together, we demonstrated that the prefrontal loss of D3Rs observed in patients may contribute to cognitive impairment by promoting adverse effects in DA signaling. Therefore, D3R agonism, and the consequential normalizing of prefrontal function, may be a therapeutic target for PD-MCI patients.
Metrics
23 File views/ downloads
26 Record Views
Details
- Title
- D3 receptor agonism attenuates deficits observed in rodents with 6-OHDA-induced medial forebrain bundle lesions
- Creators
- Courtney Anne Marshall - DU
- Contributors
- Sandhya Kortagere (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- 199 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Neurology; Drexel University
- Other Identifier
- 8257; 991014632191604721