Michael Coyle

Michael Coyle Headshot

Michael Coyle

Interrogating D3 Receptors in a Transgenic Rat Model of Parkinson’s Disease
 

This week we discuss the work of Michael Coyle, a Senior studying Integrative Neuroscience and Biochemistry. Michael joined the Summer Scholars program to pursue his study of the dopamine D3 receptor which he says is “A largely understudied receptor that appears to play a significant role in Parkinson's Disease and L-dopa-induced dyskinesia [as it] forms a heteromer complex with a receptor that elicits the opposite effect, throwing neural circuits out of balance”.

Michael’s project aims to locate the the regions of the brain that are active after D3 receptor simulation in order to identify potential ways to reduce the negative side effects of the L-dopa drug in Parkinson’s patients. Using genetically modified Parkinsonian Rats, Coyle treated Parkinson’s disease with the L-dopa drug and observed the dyskinesia (involuntary muscle spasms) that the rats expressed. He then gave half of the subjects a single dose of the dopamine D3 receptor agonist to react with the D3 receptor that was released in response to the L-dopa drug. To the control, he injected only distilled water. Coyle collected brain tissue samples and stained them, a process designed to help make the active regions of the brain more easily visible and distinguishable. Finally Coyle mounted the samples on microscope slides and compared the active cells of agonist treated samples to the untreated samples to determine the effects of D3.

The results support his hypothesis and confirm that there is a difference in the tissue sections between the experimentally treated and untreated samples. “...We found that there was a difference between experimentally treated vs untreated tissue sections, meaning that my hypothesis was correct! Upon first viewing the slides, I was literally jumping and yelling in the lab with excitement.” Coyle’s study is still underway and he is currently expanding his sample size and working to finish his staining procedures.


Next semester, after we've identified the affected brain regions, we will target those individual regions with a drug capable of temporarily inhibiting these regions alone, allowing us to see its role in L-dopa-induced, and D3R agonist-induced dyskinesia.