Neurochemical phenotypes of myenteric neurons in the rhesus monkey

Abstract

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.

Neurotoxin-Induced Catecholaminergic Loss in the Colonic Myenteric Plexus of Rhesus Monkeys

“…TH positive neurons appeared to be a minority of those present in the myenteric plexus, with only 23% of average ganglion area exhibiting TH-ir in normal control animals (Figure 2 and Supplementary Table 3), similar to previous descriptions in humans and rhesus monkeys [13,25]. In the myenteric plexus of all animals TH-ir was present mainly in neuronal processes, appearing morphologically punctate or strand like, representing processes cut at transverse or longitudinal orientations.…”

“…Loss of myenteric catecholaminergic innervation and not simply a downregulation in TH protein expression levels, was confirmed in our study by AADC immunostaining. Previous reports indicate that in mammals about 5–10% of total colonic myenteric plexus ENS neurons are catecholaminergic [13,25] while approximately 5% are serotonergic [35]. As AADC is a marker of both catecholaminergic and serotonergic neurons, the 61.7% loss of AADC-ir observed in the 6-OHDA-treated monkeys is in agreement with the near complete loss of catecholaminergic innervation.…”

“…The area of each ganglion was measured using NIH Image J software, the number of cells with nuclear HuC/D-ir was counted and then the neuron density per ganglion calculated. Abercrombie correction [25] was not applied, as this methodology overcorrects cell counts in tissue sections thinner than the object being counted [26–28]. …”

Nitric oxide

“…A significant proportion of myenteric motor neurons and interneurons, particularly those in the colon and rectum, express nNOS; this suggests NO is important for maintenance of normal colon motility, colonic reflexes, and defecation. 48 CLINICAL CORRELATIONS NO acts as "Janus molecule" that can exert either neuroprotective or neurotoxic effects according to its concentration and the cellular environment. 1,2 In general, low, transient increases in NO exert neuroprotective and antiapoptotic effects, primarily via sGC-cGMP pathway.…”

Autonomic involvement in Parkinson's disease: Pathology, pathophysiology, clinical features and possible peripheral biomarkers

“…The ENS contains different types of neurons that mediate local reflexes controlling gastrointestinal motility and secretion [41][42][43]. The primary excitatory enteric motor neurons and interneurons utilize acetylcholine [44]; neurons that express VIP and/or NO elicit smooth muscle relaxation; and submucosal VIP neurons also stimulate intestinal secretion [45]. A small percentage of myenteric neurons are dopaminergic and may inhibit intestinal motility [46].…”