Hypoganglionosis in the gastric antrum causes delayed gastric emptying

Abstract

Background Enteric nervous system (ENS) abnormalities have been implicated in delayed gastric emptying but studies exploring potential treatment options are limited by the lack of an experimental animal model. We examined the ENS abnormalities in the mouse stomach associated with aging, developed a novel model of gastroparesis, and established a new approach to measure gastric emptying. Methods A modified gastric emptying assay was developed, validated in nNOS −/− mice, and tested in mice at multiple ages. Age‐related changes in ENS structure were analyzed by immunohistochemistry. Gastric aganglionosis was generated in Wnt1‐iDTR mice using focal administration of diphtheria toxin (DT) into the anterior antral wall. Key Results Older mice (>5 months) exhibit hypoganglionosis in the gastric antrum and a decreased proportion of nNOS neurons as compared to younger mice (age 5‐7 weeks). This was associated with a significant age‐dependent decrease in liquid and solid gastric emptying. A novel model of gastric antrum hypoganglionosis was established using neural crest‐specific expression of diphtheria toxin receptor. In this model, a significant reduction in liquid and solid gastric emptying is observed. Conclusions & Inferences Older mice exhibit delayed gastric emptying associated with hypoganglionosis and a reduction in nNOS‐expressing neurons in the antrum. The causal relationship between antral hypoganglionosis and delayed gastric emptying was verified using a novel experimental model of ENS ablation. This study provides new information regarding the pathogenesis of delayed gastric emptying and provides a robust model system to study this disease and develop novel treatments.

Effects of the long-term influence of bisphenol A and bisphenol S on the population of nitrergic neurons in the enteric nervous system of the mouse stomach

“…The number of these neurons differs depending on animal species, the segment of the GI tract and the type of enteric ganglia studied 20 , 25 – 29 . Moreover, in most cases, including the mouse stomach, the population of nitrergic enteric neurons is relatively numerous 20 , 28 – 31 .…”

Autologous cell transplantation for treatment of colorectal aganglionosis in mice

“…We and others have previously shown successful isolation and expansion of ENSCs from mouse and human intestine and demonstrated their ability to engraft and differentiate into neurons and glial cells following allotransplantation or xenotransplantation into mouse models of enteric neuropathies 8 , 10 , 16 , 21 , 36 . These observations serve as proof of concept that cell therapy can be a promising therapeutic approach to replace missing or damaged enteric neurons to restore GI function 4 , 37 .…”

Electroacupuncture at ST36 Improve the Gastric Motility by Affecting Neurotransmitters in the Enteric Nervous System in Type 2 Diabetic Rats

“…ey found that the number of nerve fibers in the round and longitudinal muscle layers was normal in sections from patients with well controlled DM, while the number of nerve fibers in patients with poorly controlled DM decreased by 40-50%. Baker et al [39] established an ENS absorption model by local ablation of the anterior gastric antrum in mice. Delayed gastric emptying of solid and liquid was observed in the model mice, which was thought to be directly related to the loss of neurons.…”