An enteroendocrine cell-enteric glia connection revealed by 3D electron microscopy.

Abstract

The enteroendocrine cell is the cornerstone of gastrointestinal chemosensation. In the intestine and colon, this cell is stimulated by nutrients, tastants that elicit the perception of flavor, and bacterial by-products; and in response, the cell secretes hormones like cholecystokinin and peptide YY--both potent regulators of appetite. The development of transgenic mice with enteroendocrine cells expressing green fluorescent protein has allowed for the elucidation of the apical nutrient sensing mechanisms of the cell. However, the basal secretory aspects of the enteroendocrine cell remain largely unexplored, particularly because a complete account of the enteroendocrine cell ultrastructure does not exist. Today, the fine ultrastructure of a specific cell can be revealed in the third dimension thanks to the invention of serial block face scanning electron microscopy (SBEM). Here, we bridged confocal microscopy with SBEM to identify the enteroendocrine cell of the mouse and study its ultrastructure in the third dimension. The results demonstrated that 73.5% of the peptide-secreting vesicles in the enteroendocrine cell are contained within an axon-like basal process. We called this process a neuropod. This neuropod contains neurofilaments, which are typical structural proteins of axons. Surprisingly, the SBEM data also demonstrated that the enteroendocrine cell neuropod is escorted by enteric glia--the cells that nurture enteric neurons. We extended these structural findings into an in vitro intestinal organoid system, in which the addition of glial derived neurotrophic factors enhanced the development of neuropods in enteroendocrine cells. These findings open a new avenue of exploration in gastrointestinal chemosensation by unveiling an unforeseen physical relationship between enteric glia and enteroendocrine cells.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1371/journal.pone.0089881

Publication Info

Bohórquez, Diego V, Leigh A Samsa, Andrew Roholt, Satish Medicetty, Rashmi Chandra and Rodger A Liddle (2014). An enteroendocrine cell-enteric glia connection revealed by 3D electron microscopy. PLoS One, 9(2). p. e89881. 10.1371/journal.pone.0089881 Retrieved from https://hdl.handle.net/10161/9382.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Bohorquez

Diego V. Bohorquez

Associate Professor in Medicine

I am a gut-brain neuroscientist.

Though my initial studies focused on GI physiology and nutrition, my expertise evolved to include neuroscience following the many personal stories, which have carefully sharpened my career vision along the way.  While pursuing a Doctoral degree in Nutrition, a friend shared her struggles with obesity and gastric bypass surgery.  

Surgery was a last resort but helped to reduced her body weight dramatically and resolved her diabetes.  Yet, the most striking part of her story for me was that her perception of taste had been markedly transformed. Reshaping her gut caused her brain to convert a prior repulsion at the appearance of runny egg yolk into a strong craving to eat those same eggs.

Today, we are still a long way from understanding the full details of these intriguing conversations between our gut and our brain. But, the more we understand, the closer we are getting to treating disorders involving alterations in the perception of food in our gut.

My focus is to unveil how the brain perceives what the gut feels, how food in the intestine is sensed by our body, and how a sensory signal from a nutrient is transformed into an electrical signal that alters behavior.

Liddle

Rodger Alan Liddle

Professor of Medicine

Our laboratory has two major research interests:

Enteroendocrine Cell Biology

Enteroendocrine cells (EECs) are sensory cells of the gut that send signals throughout the body.  They have the ability to sense food and nutrients in the lumen of the intestine and secrete hormones into the blood.  Our laboratory has had a longstanding interest in two types of EECs that regulate satiety and signal the brain to stop eating.   Cholecystokinin (CCK) is secreted from EECs of the upper small intestine and regulates the ingestion and digestion of food through effects on the stomach, gallbladder, pancreas and brain.  Peptide YY (PYY) is secreted from EECs of the small intestine and colon and regulates satiety.  We recently demonstrated that CCK and PYY cells not only secrete hormones but are directly connected to nerves through unique cellular processes called ‘neuropods’.  Our laboratory is devoted to understanding EECs signaling and its role in disease.

Pancreatitis

Pancreatitis is an inflammatory disease of the pancreas compounded by intrapancreaatic activation of digestive enzymes.  Our laboratory is studying the influence of nerves on the development of pancreatitis. Neurogenic inflammation results from the release of bioactive substances from sensory neurons in the pancreas causing vasodilatation, edema, and inflammatory cell infiltration producing tissue necrosis. Our goal is to identify the agents that activate sensory neurons, characterize the receptors on sensory nerves that mediate these actions, and determine the effects of neural stimulation on pancreatic injury with the long-term objective of developing strategies to reduce neurogenic inflammation to treat pancreatitis. 

Visit our lab page.


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.