Investigator:
Mariangela Scarduzio, PhD
Name of Institution:
University of Alabama at Birmingham
Project Title:
Striatal acetylcholine dynamics in L-DOPA-induced dyskinesia
Investigator Bio:
Dr. Scarduzio is an Electrophysiologist and Assistant Professor at the Center for Neurodegeneration and Experimental Therapeutics (CNET) in the Department of Neurology at the University of Alabama at Birmingham (UAB). Her research is focused on deciphering the striatal circuitry governing basal ganglia-related movement disorders with a particular focus on the role of striatal neuromodulators (acetylcholine and dopamine) in movement regulation.
Dr. Scarduzio received her PhD in Neurophysiology and Electrophysiology from the University of Perugia in Italy and trained as a Postdoctoral Fellow at the University of Perugia and Northwestern University with Drs. Paolo Calabresi and James Surmeier, respectively. Her background in patch-clamp electrophysiology laid a foundation to assess the fundamental mechanisms underpinning basal ganglia-related movement disorders at the cellular, synaptic and circuit levels. Recent developments have expanded her research beyond these realms to encompass system-level investigations, employing advanced in vivo imaging techniques in mouse models of dystonia, Parkinson’s disease (PD), Huntington’s disease and levodopa (L-DOPA)-induced dyskinesia (LID).
Objective:
To investigate how L-DOPA-induced fluctuating levels of the neurotransmitter dopamine (DA) affect the levels of acetylcholine (ACh), another neurotransmitter involved in movement regulation in the dorsal striatum, the part of the brain responsible for PD and LID symptoms.
Background:
Understanding genetic forms of PD have unveiled biological mechanisms that are relevant to non-genetic forms of PD as well. I identified PSMF1 as a new gene associated with early-onset PD and parkinsonism in multiple families. The function of PSMF1 in neurons is unknown.
Methods/Design:
The project will focus on how striatal ACh spontaneous oscillations evolve as DA levels decrease, and LID develops in a mouse model of PD. We will employ a new technique that allows for monitoring of brain ACh release in real time, as the living animal moves freely, and its movements can be quantified. We hypothesize that in brains lacking DA, the replacement of DA with L-DOPA causes distortion of the natural rhythm of ACh in the striatum, leading to LID.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
By uncovering ACh transmission alterations, their causes, and their relationship to movement execution, we hope to provide insights into potential therapeutic strategies, including both medications and neuromodulatory techniques, for managing movement difficulties associated with PD and LID.