Neuropod Cells: The Emerging Biology of Gut-Brain Sensory Transduction

Abstract

<jats:p> Guided by sight, scent, texture, and taste, animals ingest food. Once ingested, it is up to the gut to make sense of the food's nutritional value. Classic sensory systems rely on neuroepithelial circuits to convert stimuli into signals that guide behavior. However, sensation of the gut milieu was thought to be mediated only by the passive release of hormones until the discovery of synapses in enteroendocrine cells. These are gut sensory epithelial cells, and those that form synapses are referred to as neuropod cells. Neuropod cells provide the foundation for the gut to transduce sensory signals from the intestinal milieu to the brain through fast neurotransmission onto neurons, including those of the vagus nerve. These findings have sparked a new field of exploration in sensory neurobiology—that of gut-brain sensory transduction. </jats:p>

Cannabinoid CB1 Receptors in the Intestinal Epithelium Are Required for Acute Western-Diet Preferences in Mice

“…Cholecystokinin is secreted from enteroendocrine cells in the upper small-intestinal epithelium when nutrients arrive in the lumen, and transmits satiation signals to the brain by interacting with cholecystokinin A receptors on the afferent vagus nerve [30,40,[47][48][49][50] and possibly the brain [51,52]. Bohorquez and colleagues recently characterized enteroendocrine cells (i.e., neuropods) in the mouse intestinal epithelium that form functional synapses with afferent vagal fibers [33]. Neuropods sense nutrients in the lumen and in response, release glutamate and cholecystokinin, which activate afferent vagal neurons in a coordinated manner [53].…”

“…Nutrients are sensed by gustatory cells in the oral cavity and enteroendocrine cells in the intestinal epithelium. In response, these cells release several satiation-and satiety-related molecules that communicate with the brain via a mechanism that includes the afferent vagus nerve [30][31][32][33][34][35][36][37][38]. We recently reported that eCB signaling in the gut controls nutrient-induced release of satiation peptides [16].…”

Gut peptides and the microbiome: focus on ghrelin

“…Neuropods are basal processes of EECs that contain large, dense vesicles of gut peptides and small, clear vesicles containing neurotransmitters [ 27 , 28 ]. These features extend into the lumen and interact with vagal neurons via release of vesicle contents for rapid signal transduction to the brain [ 29 ]. Thus, the interaction of gut peptides with the gut–brain axis orchestrates metabolic function, communicates nutrient status to the brain and modulates central-regulated appetite and homeostatic processes, which together drive food seeking and eating behaviour, to maintain energy balance.…”

Less Is More: Rare Pulmonary Neuroendocrine Cells Function as Critical Sensors in Lung

“…These highly heterogeneous enteroendocrine subtypes facilitate specific metabolic and immune responses to different inputs from ingested nutrients, irritants, pathogens, etc. (Kaelberer et al, 2020;Yu et al, 2020). To investigate the potential mechanisms that control enteroendocrine cell diversification, a recent study combined scRNA-seq technique and the expression of fluorescent timer proteins in the enteroendocrine lineage.…”