Investigator:
Karen L. Eskow Jaunarajs, PhD
Name of Institution:
University of Alabama at Birmingham, Birmingham, AL
Project Title:
A cell type-specific transcriptional profile of the development of L-DOPA-induced dyskinesia
Investigator Bio:
Dr. Jaunarajs is an Instructor in Neurology in the Center for Neurodegeneration and Experimental Therapeutics at the University of Alabama at Birmingham. Dr. Jaunarajs obtained a BS in Psychobiology from Binghamton University in 2006 and remained there to pursue a PhD in Neurobiology in 2011 under the mentorship of Dr. Christopher Bishop. Her dissertation focused on the role of the serotonergic system on the motor and non-motor side effects associated with dopamine replacement therapy in a model of Parkinson’s disease (PD) and was the recipient of the Graduate Student Excellence in Research Award. Dr. Jaunarajs received post-doctoral training in the laboratory of Dr. David Standaert at the University of Alabama at Birmingham, investigating cholinergic dysfunction across multiple models of genetic dystonias. Her current research interests relate to striatal circuitry and neurochemistry of movement disorders, particularly PD and dystonia
Objective:
To understand changes in gene expression within each cell sub-type found in motor areas of the brain and how they evolve over the course of the development and expression of L-DOPA-induced dyskinesias.
Background:
Individuals with PD are often treated chronically with L-DOPA to improve motor symptoms. However, neurodegeneration of dopamine neurons coupled with repeated “highs and lows” of dopamine in the striatum from L-DOPA treatment can lead to the development of L-DOPA-induced dyskinesias. This response appears to be a form of motor learning, resulting in dopamine-induced changes in multiple types of brain cells. Precisely how these changes occur over time in individual subtypes of cells remains a mystery. To shed light on this process, we are exploring changes in gene expression utilizing a new technique called single-nuclei RNA sequencing, allowing us to understand the time-course of changes in gene expression at the level of a single cell.
Methods/Design:
We will expose a well-characterized mouse model of PD to L-DOPA over time to induce dyskinesias and then investigate the cell-type specific changes in gene expression that take place. We will characterize which genes are expressed in which cells over the time course of l-DOPA exposure and development of dyskinesias.
Relevance to Diagnosis/Treatment of Parkinson’s disease:
L-DOPA-induced dyskinesias are one of the most significant factors that impacts the quality of life of people with PD. This project aims to understand the details of cellular changes as dyskinesias are developing and will thereby provide knowledge of appropriate targets for halting the motor learning underlying the development of dyskinesias.