Evaluation of A Nitric Oxide Synthase Inhibitor in a Drosophila Model of L-Dopa Induced Dyskinesia
Advisor Information
Bruce Chase
Location
Dr. C.C. and Mabel L. Criss Library
Presentation Type
Poster
Start Date
4-3-2016 12:45 PM
End Date
4-3-2016 2:15 PM
Abstract
Parkinson’s Disorder (PD) is a neurodegenerative disorder that affects 2-5% of the population. It is characterized by the loss of dopaminergic neurons in the substantia nigra (SN). These include loss of fine motor control, tremors, slowness of movement, and postural instability. Dopaminergic neurons and their pathways are evolutionary ancient. These conserved pathways allow investigations using Drosophila melanogaster (fruit flies) to serve as models for investigating PD. One of the most widely used treatments for PD is dopamine replacement therapy: levodopa is used to alleviate the symptoms of dopaminergic loss. Levodopa serves as a precursor that is able to pass the blood brain barrier and can be synthesized into usable neurotransmitter. One effect of chronic use of levodopa is dyskinesia, which is characterized by uncontrollable and erratic motor function since all PD patients do not develop levodopa-induced dyskinesia (LID), this work hypothesizes that it is partly due to a quantitative genetic trait that is variable across the population. The role of neuroinflammation was indirectly assessed through the use of anti-diskinetic medication, amantadine, which alleviates the effects LID by acting on microglia, where nitric oxide (NO) is thought to be involved. 5 That study discovered that 7-nitroindazole/ (7-NI) works to inhibit nitric oxide synthase (NOS) without altering L-dopa motor improvements. I have undertaken research to ask whether 7-NI can modify LID-like behavior in flies, and if so, work towards identifying the responsible genes.
Evaluation of A Nitric Oxide Synthase Inhibitor in a Drosophila Model of L-Dopa Induced Dyskinesia
Dr. C.C. and Mabel L. Criss Library
Parkinson’s Disorder (PD) is a neurodegenerative disorder that affects 2-5% of the population. It is characterized by the loss of dopaminergic neurons in the substantia nigra (SN). These include loss of fine motor control, tremors, slowness of movement, and postural instability. Dopaminergic neurons and their pathways are evolutionary ancient. These conserved pathways allow investigations using Drosophila melanogaster (fruit flies) to serve as models for investigating PD. One of the most widely used treatments for PD is dopamine replacement therapy: levodopa is used to alleviate the symptoms of dopaminergic loss. Levodopa serves as a precursor that is able to pass the blood brain barrier and can be synthesized into usable neurotransmitter. One effect of chronic use of levodopa is dyskinesia, which is characterized by uncontrollable and erratic motor function since all PD patients do not develop levodopa-induced dyskinesia (LID), this work hypothesizes that it is partly due to a quantitative genetic trait that is variable across the population. The role of neuroinflammation was indirectly assessed through the use of anti-diskinetic medication, amantadine, which alleviates the effects LID by acting on microglia, where nitric oxide (NO) is thought to be involved. 5 That study discovered that 7-nitroindazole/ (7-NI) works to inhibit nitric oxide synthase (NOS) without altering L-dopa motor improvements. I have undertaken research to ask whether 7-NI can modify LID-like behavior in flies, and if so, work towards identifying the responsible genes.