Evaluation of the Enteric Nervous System in PD

Objective/Rationale:
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.

Project Description:
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.
Anticipated Outcome:
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.