Evaluation of the Enteric Nervous System in PD
Clinicopathological Correlations of Parkinsonís Disease, 2009
Gastrointestinal (GI) symptoms (constipation, for example) afflict essentially every PD patient, negatively impact quality of life, and diminish effectiveness of oral medications. Poor understanding of the root cause(s) of GI dysfunction in PD has limited attempts to study these phenomena experimentally and hindered development of effective therapeutic agents. Recently, it has been proposed that abnormalities in the enteric nervous system, a semi-independent network of nerves lining the digestive tract, may cause GI symptoms in PD.
We will examine the enteric nervous system in postmortem tissue samples from patients with PD and compare them to samples from unaffected individuals. (Samples will be provided by the Arizona Parkinson's Disease Consortium.) Specifically, we will determine whether or not there is nerve cell loss in the gut, as there is in the brain in Parkinson’s. Additionally, we will determine whether or not any loss is selective for a particular type of nerve cell. We will also examine another pathological hallmark of Parkinson’s, the Lewy body, to determine if particular types of enteric nerves are vulnerable to that damage. Finally, we will determine if any damage observed was associated with clinical symptoms of Parkinson’s.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Treating GI symptoms in patients with Parkinson’s can be very difficult, and standard approaches are frequently ineffective. Better understanding of the cause of these symptoms is critical to developing more advanced and effective treatments. Discovery of a particular type of nerve cell damage in the gut from Parkinson’s patients could directly lead to new drug treatment options. In addition, understanding of the effects of Parkinson’s on nerve cells beyond those typically studied is critical to understanding its cause.
We anticipate generating a careful anatomical description of the effects of Parkinson’s on the gut that will serve as a benchmark for evaluating new treatment options of GI symptoms (constipation, motor fluctuations), for modeling Parkinson’s in experimental systems (cells or animals), and for understanding the broader effects of Parkinson’s on the entire nervous system.
INTERIM PROGRESS REPORT
Preliminary results suggest that PD does not cause cell loss in the network of neurons (enteric nervous system) that controls digestive function. However, cell damage is apparent from accumulation of the PD-related protein alpha-synuclein in the gastrointestinal (GI) tract. The distribution of synuclein accumulation in the GI tract agrees with previous reports and suggests a role for the vagus nerve (one of two extremely long cranial nerves that run from the brain to the abdomen) in its accumulation More detailed experiments are ongoing to provide more information in that regard.
Presentations & Publications
2011 Clinical and Pathological Features of Gastrointestinal Dysfunction in Parkinson’s Disease, University of Florida Dept. of Neurology Grand Rounds
2010 Parkinsonism in the gastrointestinal tract: an open window in mice and man, Emory University Dept of Physiology
2010 American Society for Neural Therapy and Repair. Clearwater, FL, “Parkinsonism in the gastrointestinal tract: an open window in mice and man"
2010 World Parkinson’s Congress. Glasgow, Scotland, “Involvement of the gastrointestinal tract in PD”
Assistant Professor, Department of Neurology at Emory University School of Medicine