Morphological and immunohistochemical changes in the enteric nervous system of normal and inflamed intestine

The autonomic nervous system consists of three divisions defined as sympathetic, parasympathetic, and enteric. The neural crest cell-derived enteric nervous system (ENS) is a complex neural network embedded in the wall of the gastrointestinal tract that regulates the intestinal reflex behaviors and represents an intrinsic innervation acting independently respect to the central nervous system (CNS) input. The ENS has two ganglionated plexuses, the myenteric and the submucosal plexuses, in which almost all intrinsic nervous cells are located (1). The submucosal plexus is prominent only in the small and large intestines. The myenteric plexus extends the full length of the digestive tract, between the outer longitudinal and circular muscle layers, from the esophagus to the rectum. The myenteric plexus is composed of neurons surrounded by a barrier consisting of proteins and enteric glial cells: the encapsulated ganglia connected by interganglionic segments (2). Our aim is to investigate and characterize the changes between normal and inflamed intestine through: (i) the morphology of the myenteric plexus using various histological techniques (Hematoxylin and Eosin, Masson’s Trichrome and Silver Impregnation), and (ii) immunohistochemical expression of the main enteric neurotransmitters and glial markers, to characterize respectively neuron (ChAT, alfa-Syn, Vip, TH), glia (GFAP) and microglia (CD11b). Surgical specimens of small and large intestine were collected from patients with Crohn’s disease and from control patients. In this preliminary study the myenteric ganglia revealed significant differences in shape, size, neurons population, enteroglia distribution, in the microglia and in the capsule surrounding the ganglia. Recent study in the myenteric plexus suggests that the ENS and CNS use similar mechanisms of neuroimmune interaction, although exposed to different environmental signals, it seems likely that both tissues produce equivalent soluble factors (3). Modified features of myenteric ganglia we found in Crohn disease needs further exploration, but they will probably shrink the current idiopathic category of gastrointestinal disease starting to include them in the disorders in common with the CNS and the ENS, the so-called brain–gut diseases.