Classification of human enteric neurons

Abstract

Major advances in our understanding of the functional heterogeneity of enteric neurons are driven by the application of newly developed, innovative methods. In contrast to this progress, both animal and human enteric neurons are usually divided into only two morphological subpopulations, “Dogiel type II” neurons (with several long processes) and “Dogiel type I” neurons (with several short processes). This implies no more than the distinction of intrinsic primary afferent from all other enteric neurons. The well-known chemical and functional diversity of enteric neurons is not reflected by this restrictive dichotomy of morphological data. Recent structural investigations of human enteric neurons were performed by different groups which mainly used two methodical approaches, namely detecting the architecture of their processes and target-specific tracing of their axonal courses. Both methods were combined with multiple immunohistochemistry in order to decipher neurochemical codes. This review integrates these morphological and immunohistological data and presents a classification of human enteric neurons which we believe is not yet complete but provides an essential foundation for the further development of human gastrointestinal neuropathology.

Somatostatin and Its Receptor System in Colorectal Cancer

“…In the GI tract, the majority of SST production occurs in mucosa (>90%), mostly of the stomach, the duodenum, and the jejunum, with <10% taking place in the submucosal and muscle layers. In the mucosa, SST is localized in epithelial endocrine cells/enteroendocrine cells (EECs) [ 24 , 29 , 30 , 36 , 38 , 39 , 40 , 41 ]. The most abundant sources of SST in the GI tract are intestinal EECs, termed δ- or D cells in the antral and the fundic mucosa of the stomach.…”

“…In mice, K-cells located in the upper small intestine were described to overlap in 10% with GLP-1 and in 6% with SST [ 74 ]. However, the intestinal SST, as opposed to stomach SST, is produced mostly in ENS structures of the submucosal and myenteric plexuses (in Dogiel type II neurons) [ 38 , 39 , 40 ]. In the human colon, similarly to the small intestine, co-localization of SST and calretinin (CALR) indicates type II neurons as a primary source of SST.…”

“…In the human colon, similarly to the small intestine, co-localization of SST and calretinin (CALR) indicates type II neurons as a primary source of SST. However, around half of SST(+)/CALR(−) cells was also made up of neurofilament-reactive, multi-axonal type II neurons [ 40 ].…”

“…The most abundant source of SST in the GI tract is a group of highly specialized intestinal endocrine cells, known as enteroendocrine cells (EECs) restricted to the mucosa, termed D cells in the stomach [ 29 , 30 , 31 , 32 , 33 ], as well as delta (δ) cells in Langerhans islets of the pancreas [ 34 , 35 , 36 , 37 ]. SST in the GI tract is also produced by neurons of the enteric nervous system (ENS) [ 24 , 29 , 30 , 36 , 38 , 39 , 40 , 41 ]. However, the majority of the circulating SST is secreted by gastrointestinal D cells (~65%), ~30% by the CNS, and ~5% by pancreatic D (δ) cells [ 37 ].…”

The Enteric Nervous System and the Microenvironment of the Gut: The Translational Aspects of the Microbiome-Gut-Brain Axis

“…Regional differences in the connectivity of the enteric nervous system (ENS) were observed in mice between the proximal versus distal colon, as well [42]. Our knowledge of human enteric neuron classes [43,44] and circuits [45] is much more limited due to the restricted access to human tissues. It is not possible to get a general picture-among other reasons-because of the differences between species.…”