Gastrointestinal dysfunction is a prominent non-motor feature of Parkinson’s disease (PD) that contributes directly to the morbidity of patients, complicates management of motor symptoms, and may herald incipient PD in patients without motor disability. Although PD has traditionally been considered a disease of dopaminergic neurons in the substantia nigra, analyses of gastrointestinal samples from PD patients have consistently revealed pathology in the enteric nervous system (ENS). The relationship of PD pathology to GI dysmotility is poorly understood, and this lack of understanding has led to limited success in developing treatments for PD-related GI symptoms. We have quantitatively compared myenteric neuron density and relative abundance of NO, VIP, and catecholamine neurons between patients with PD and control individuals along the length of the GI tract. In addition, we have examined the frequency of GI α-synuclein neuritic pathology and its co-localization with the same neuronal markers. We have included a comparison with a small population of patients with incidental Lewy bodies (ILB) found at autopsy. These data indicate there is no neuronal loss in the myenteric plexus in PD. Lewy body pathology parallels parasympathetic autonomic input from the DMV, not the distribution of extrinsic sympathetic input or intrinsic enteric neurons, and is only rarely co-localized with tyrosine hydroxylase. These data provide a critical background to which further analyses of the effect of PD on the GI tract may be compared and suggest that neuropathology in myenteric neurons is unlikely to be a causative factor in PD-related GI dysmotility.

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Understanding the neurochemical composition of the enteric nervous system (ENS) is critical for elucidating neurological function in the gastrointestinal (GI) tract in health and disease. Despite their status as the closest models of human neurological systems, relatively little is known about enteric neurochemistry in nonhuman primates. We describe neurochemical coding of the enteric nervous system, specifically the myenteric plexus, of the rhesus monkey (Macaca mulatta) by immunohistochemistry and directly compare it to human tissues. There are considerable differences in the myenteric plexus along different segments of the monkey GI tract. While acetylcholine neurons make up the majority of myenteric neurons in the stomach (70%), they are a minority in the rectum (47%). Conversely, only 22% of gastric myenteric neurons express nitric oxide synthase (NOS) compared to 52% in the rectum. Vasoactive intestinal peptide (VIP) is more prominent in the stomach (37%) versus the rest of the GI tract (10%), and catecholamine neurons are rare (1%). There is significant coexpression of NOS and VIP in myenteric neurons that is more prominent in the proximal GI tract. Taken as a whole, these data provide insight into the neurochemical anatomy underlying GI motility. While overall similarity to other mammalian species is clear, there are some notable differences between the ENS of rhesus monkeys, humans, and other species that will be important to take into account when evaluating models of human diseases in animals.