Cited by 236Gastrointestinal motility and disordersIon Channels and ReceptorsBiochemical Analysis and Sensing Techniques

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

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Kaelberer, Melanie Maya, Rupprecht, Laura E., Liu, Winston W., Weng, Peter, Bohórquez, Diego V.·2020·Annual Review of Neuroscience

DOI 10.1146/annurev-neuro-091619-022657PMC PMC7573801

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Abstract

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.

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Induction of c-Fos and ΔFosB Immunoreactivity in Rat Brain by Vagal Nerve Stimulation
Cunningham, J. T., Mifflin, S. W., Gould, G. G., & Frazer, A. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301570 · Cited by 158 · cited 1×
“The labeling is absent when the vagus is severed (Cunningham et al. 2008).”
Background
Density distribution of free fatty acid receptor 2 (FFA2)-expressing and GLP-1-producing enteroendocrine L cells in human and rat lower intestine, and increased cell numbers after ingestion of fructo-oligosaccharide
Kaji, I., Karaki, S.-I., Tanaka, R., & Kuwahara, A. (2010) · Journal of Molecular Histology · doi:10.1007/s10735-010-9304-4 · Cited by 155 · cited 1×
“For example, when SCFA precursors are introduced to the gut lumen, the number of peptide YY enteroendocrine cells that express FFAR2 increases (Kaji et al. 2011).”
Background
Untersuchungen über den Bau der Labdrüsen
Heidenhain, R. (1870) · Archiv für Mikroskopische Anatomie · doi:10.1007/bf02955986 · Cited by 151 · cited 1×
“…was postulated by histologists as early as the 1860s. Schwalbe (1867) and Lovén (1868) observed a clustering of cells on the epithelial surface of the tongue, and Heidenhain (1870) extended these observations to the intestinal epithelium and identified a group of yellow chromate–staining cells.”
Background
Activation of Enteroendocrine Cells via TLRs Induces Hormone, Chemokine, and Defensin Secretion
Palazzo, M., Balsari, A., Rossini, A., Selleri, S., Calcaterra, C., Gariboldi, S., Zanobbio, L., Arnaboldi, F., Shirai, Y. F., Serrao, G., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.7.4296 · Cited by 147 · cited 1×
“…(TLR-1, 2, 4, 5, and 9), directly sense multiple bacterial components, including peptidoglycan, LPS, flagellin, and CpG. Applying such stimuli on STC-1 cells results in cholecystokinin release and increased activity ofNF-κB,TNF, andTGFβ expression (Bogunovic et al. 2007,Palazzo et al. 2007).”
Background
Representation of the cecum in the lateral dorsal motor nucleus of the vagus nerve and commissural subnucleus of the nucleus tractus solitarii in rat
Altschuler, S. M., Ferenci, D. A., Lynn, R. B., & Miselis, R. R. (1991) · The Journal of Comparative Neurology · doi:10.1002/cne.903040209 · Cited by 147 · cited 1×
“Conversely, the distal small intestine and cecum are innervated by vagal afferents, which project terminals more rostrally in the NTS, in the commissural subnucleus (Altschuler et al. 1991, Zhang et al. 1992).”
Background
Vagal unitary responses to intestinal amino acid infusions in the anesthetized cat: A putative signal for protein induced satiety
Jeanningros, R. (1982) · Physiology & Behavior · doi:10.1016/0031-9384(82)90094-4 · Cited by 144 · cited 1×
“Studies have reported that different vagal fibers are specifically tuned for each macronutrient ( Jeanningros 1982, Lal et al. 2001,Mei 1978).”
Background
Medullary c-Fos activation in rats after ingestion of a satiating meal
Rinaman, L., Baker, E. A., Hoffman, G. E., Stricker, E. M., & Verbalis, J. G. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.275.1.r262 · Cited by 139 · cited 1×
“For example, exogenous cholecystokinin administration at doses that suppress meal size activates neurons in the AP and medial NTS (Fraser & Davison 1992, Rinaman et al. 1998).”
Background
Effects of a Diet-Based Weight-Reducing Program with Probiotic Supplementation on Satiety Efficiency, Eating Behaviour Traits, and Psychosocial Behaviours in Obese Individuals
Sánchez, M., Darimont, C., Panahi, S., Drapeau, V., Marette, A., Taylor, V. H., Doré, J., & Tremblay, A. (2017) · Nutrients · doi:10.3390/nu9030284 · Cited by 138
Up-regulation of intestinal type 1 taste receptor 3 and sodium glucose luminal transporter-1 expression and increased sucrose intake in mice lacking gut microbiota
Swartz, T. D., Duca, F. A., de Wouters, T., Sakar, Y., & Covașă, M. (2011) · British Journal Of Nutrition · doi:10.1017/s0007114511003412 · Cited by 137 · cited 1×
“In addition, the receptor profile of the epithelial layers shifts to decreased numbers of FFAR2 and FFAR3 but increased expression of glucose transporters and taste receptors (Swartz et al. 2012).”
Background
Vagus nerve stimulation potentiates hippocampal LTP in freely-moving rats
Zuo, Y., Smith, D. C., & Jensen, R. A. (2007) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.11.009 · Cited by 135 · cited 1×
“Conversely, vagal nerve stimulation increases plasticity, neurogenesis (Follesa et al. 2007), and long-term potentiation in the hippocampus (Zuo et al. 2007).”
Background
Localized Release of Serotonin (5-Hydroxytryptamine) by a Fecal Pellet Regulates Migrating Motor Complexes in Murine Colon
Heredia, D. J., Dickson, E. J., Bayguinov, P. O., Hennig, G. W., & Smith, T. K. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.12.010 · Cited by 133 · cited 1×
“Indeed, serotonin release promotes gut motility (Heredia et al. 2009) and the secretion of fluids into the lumen (Sidhu & Cooke 1995).”
Background
Vagus nerve stimulation improves working memory performance
Sun, L., Peräkylä, J., Holm, K., Haapasalo, J., Lehtimäki, K., Ogawa, K., Peltola, J., & Hartikainen, K. (2017) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803395.2017.1285869 · Cited by 132 · cited 1×
“Vagal nerve stimulation is also known to enhance memory (Clark et al. 1995, 1998) and improve working memory performance (Sun et al. 2017).”
Background
Integration of vagal afferent responses to gastric loads and cholecystokinin in rats
Schwartz, G. J., McHugh, P. R., & Moran, T. H. (1991) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1991.261.1.r64 · Cited by 127
Selective effects of vagal deafferentation and celiac–superior mesenteric ganglionectomy on the reinforcing and satiating action of intestinal nutrients
Sclafani, A. J., Ackroff, K., & Schwartz, G. J. (2003) · Physiology & Behavior · doi:10.1016/s0031-9384(02)00968-x · Cited by 118 · cited 1×
“Vagal deafferentation failed to block gut-stimulated conditioning of a neutral sweet flavor (Sclafani et al. 2003).”
Background
Role for 5-HT and ACh in submucosal reflexes mediating colonic secretion
Sidhu, M., & Cooke, H. J. (1995) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1995.269.3.g346 · Cited by 115 · cited 1×
“Indeed, serotonin release promotes gut motility (Heredia et al. 2009) and the secretion of fluids into the lumen (Sidhu & Cooke 1995).”
Background
Mechanisms of activation of mouse and human enteroendocrine cells by nutrients
Symonds, E. L., Peiris, M., Page, A. J., Chia, B., Dogra, H., Masding, A., Galanakis, V., Atiba, M., Bulmer, D. C., Young, R. L., et al. (2014) · Gut · doi:10.1136/gutjnl-2014-306834 · Cited by 114 · cited 1×
“…shown that CaSR,GPRC6A, andLPR5 are general protein sensors that induce the secretion of peptides (e.g., cholecystokinin, glucagon-like peptide 1, serotonin, or peptide YY) following receptor binding (Gribble&Reimann 2016,Kokrashvili et al. 2009, SantosHernandez et al. 2018, Symonds et al. 2015).”
Background
Pathways of Fos expression in locus ceruleus, dorsal vagal complex, and PVN in response to intestinal lipid
Mönnikes, H., Lauer, G., Bauer, C., Tebbe, J. J., Zittel, T. T., & Arnold, R. (1997) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1997.273.6.r2059 · Cited by 113 · cited 8×
“Using a combinatorial viral approach, Han et al. (2018) showed that terminals from the right nodose ganglion project to the ventromedial NTS, whereas those of the left nodose ganglion end in the AP.”
BackgroundInfluential
CD36‐dependent signaling mediates fatty acid‐induced gut release of secretin and cholecystokinin
Sundaresan, S., Shahid, R. A., Riehl, T. E., Chandra, R., Nassir, F., Stenson, W. F., Liddle, R. A., & Abumrad, N. A. (2012) · The FASEB Journal · doi:10.1096/fj.12-217703 · Cited by 112 · cited 1×
“Global CD36 knockout mice demonstrate impaired hormone secretion (Sundaresan et al. 2013).”
Background
Intraduodenal infusions of fats elicit satiety in sham-feeding rats
Greenberg, D., Smith, G. P., & Gibbs, J. (1990) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1990.259.1.r110 · Cited by 105 · cited 1×
“F or p er so na l u se o nl y. in rats in which the food entering the stomach is bypassed using a gastric fistula, called sham feeding (Greenberg et al. 1990).”
Background
Hippocampal lesions impair retention of discriminative responding based on energy state cues.
Davidson, T. L., Kanoski, S. E., Chan, K., Clegg, D. J., Benoit, S. C., & Jarrard, L. E. (2010) · Behavioral Neuroscience · doi:10.1037/a0018402 · Cited by 102 · cited 1×
“Rats with lesions to the hippocampus, a brain region associated with memory, have impaired memory for food-related cues (Davidson et al. 2010).”
Background
Intestinal Signaling of Proteins and Digestion-Derived Products Relevant to Satiety
Santos-Hernández, M., Miralles, B., Amigo, L., & Recio, I. (2018) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.8b02355 · Cited by 100
Cholecystokinin‐induced c‐fos expression in the rat brain stem is influenced by vagal nerve integrity
Fraser, K. A., & Js, D. (1992) · Experimental Physiology · doi:10.1113/expphysiol.1992.sp003579 · Cited by 97 · cited 8×
“Using a combinatorial viral approach, Han et al. (2018) showed that terminals from the right nodose ganglion project to the ventromedial NTS, whereas those of the left nodose ganglion end in the AP.”
BackgroundInfluential
TLR ligands and butyrate increasePyyexpression through two distinct but inter-regulated pathways
Larraufie, P., Dore, J. M., Lapaque, N., & Blottière, H. M. (2016) · Cellular Microbiology · doi:10.1111/cmi.12648 · Cited by 97 · cited 1×
“Moreover, MAMP application increased peptide YY expression in a human cecal cell line in an NF-κB-dependent manner (Larraufie et al. 2017).”
Background
Release of Endogenous Opioids From Duodenal Enteroendocrine Cells Requires Trpm5
Kokrashvili, Z., Rodriguez, D., Yevshayeva, V., Zhou, H., Margolskee, R. F., & Mosinger, B. J. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.02.070 · Cited by 90 · cited 2×
“…shown that CaSR,GPRC6A, andLPR5 are general protein sensors that induce the secretion of peptides (e.g., cholecystokinin, glucagon-like peptide 1, serotonin, or peptide YY) following receptor binding (Gribble&Reimann 2016,Kokrashvili et al. 2009, SantosHernandez et al. 2018, Symonds et al. 2015).”
Background
Responses of celiac and cervical vagal afferents to infusions of lipids in the jejunum or ileum of the rat
Randich, A., Tyler, W. J., Cox, J. E., Meller, S. T., Kelm, G. R., & Bharaj, S. S. (2000) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2000.278.1.r34 · Cited by 89 · cited 1×
“Multiunit recordings of the celiac and the cervical vagus nerve have demonstrated increased firing rate following ileal and jejunal infusion of fatty acids (Randich et al. 2000).”
Background
Single-cell RNA-sequencing reveals a distinct population of proglucagon-expressing cells specific to the mouse upper small intestine
Glasssmith, L. L., Calero‐Nieto, F. J., Jawaid, W., Larraufie, P., Kay, R. G., Göttgens, B., Reimann, F. M., & Gribble, F. M. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.07.014 · Cited by 89 · cited 1×
“In fact, a single cell can contain transcripts for both satiety- and hunger-inducing hormones (Glass et al. 2017).”
Background
Gastric volume detection after selective vagotomies in rats
Phillips, R. J., & Powley, T. L. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.274.6.r1626 · Cited by 85 · cited 1×
“In rats equipped with pyloric cuffs,which restrict volume to the stomach, gastric preloads suppressed meal size in a volume-dependent manner (Phillips & Powley 1998).”
Background
Suppression of meal size by intestinal nutrients is eliminated by celiac vagal deafferentation
Walls, E. K., Phillips, R. J., Wang, F., Holst, M., & Powley, T. L. (1995) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1995.269.6.r1410 · Cited by 84 · cited 1×
“This nutrient-induced suppression of sham feeding is attenuated by vagotomy (Walls et al. 1995, Yox et al. 1991).”
Background
Fos protein expression in the nucleus of the solitary tract in response to intestinal nutrients in awake rats
Zittel, T. T., GIORGIO, R. D., Sternini, C., & Raybould, H. E. (1994) · Brain Research · doi:10.1016/0006-8993(94)91272-6 · Cited by 83 · cited 1×
“Intraduodenal infusions of macronutrients result in significant c-Fos expression in the area postrema (AP) and in the medial, dorsal, and rostral commissural regions of the NTS (Monnikes et al. 1997, Phifer & Berthoud 1998, Zittel et al. 1994).”
Background
Vagotomy attenuates suppression of sham feeding induced by intestinal nutrients
Yox, D. P., Stokesberry, H., & Ritter, R. C. (1991) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1991.260.3.r503 · Cited by 79 · cited 8×
“Using a combinatorial viral approach, Han et al. (2018) showed that terminals from the right nodose ganglion project to the ventromedial NTS, whereas those of the left nodose ganglion end in the AP.”
BackgroundInfluential
Disruption of brain stimulation-induced feeding by dopamine receptor blockade
Phillips, A. G., & NIKAIDO, R. S. (1975) · Nature · doi:10.1038/258750a0 · Cited by 78 · cited 1×
“Phillips & Nikaido (1975) showed that stimulating the LH, a brain area involved in reward, induces voracious feeding, an effect that is abolished when the vagus nerve is severed (Ball 1974).”
Background
Protein hydrolysate-induced cholecystokinin secretion from enteroendocrine cells is indirectly mediated by the intestinal oligopeptide transporter PepT1
Liou, A. P., Chavez, D., Espero, E., Hao, S., Wank, S. A., & Raybould, H. E. (2011) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00521.2010 · Cited by 77 · cited 2×
“In addition to GPR119, intestinal enteroendocrine cells express FFAR1 and FFAR4,which are GPCRs coupled to a Gαq subunit (Liou et al. 2011b).”
Background
Ultrastructural evidence for an innervation of epithelial enterochromaffine cells in the guinea pig duodenum
Lundberg, J. M., Dahlström, A. B., Bylock, A. L., Ahlman, H., Pettersson, G., Larsson, I., Hansson, H., & Kewenter, J. (1978) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1978.tb06245.x · Cited by 76 · cited 1×
“Lundberg et al. (1978) reported one micrograph in which the closest neuron was 100 nm away from an enterochromaffin cell.”
Background
Integration of vagal afferent responses to duodenal loads and exogenous CCK in rats
Schwartz, G. J., Tougas, G. H., & Moran, T. H. (1995) · Peptides · doi:10.1016/0196-9781(95)00033-g · Cited by 73 · cited 1×
“There have been additional reports of duodenal distension activating vagal afferent nerve activity (Schwartz et al. 1995).”
Background
Duodenal nutrient infusions differentially affect sham feeding and Fos expression in rat brain stem
Phifer, C. B., & Berthoud, H. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.274.6.r1725 · Cited by 68 · cited 1×
“Intraduodenal infusions of macronutrients result in significant c-Fos expression in the area postrema (AP) and in the medial, dorsal, and rostral commissural regions of the NTS (Monnikes et al. 1997, Phifer & Berthoud 1998, Zittel et al. 1994).”
Background
Stages in the recovery of feeding following vagotomy in rabbits
Rezek, M., Vanderweele, D. A., & Novin, D. (1975) · Behavioral Biology · doi:10.1016/s0091-6773(75)90338-7 · Cited by 67 · cited 1×
“Consistent with this, vagus nerve stimulation is thought to reduce food intake, although the vagus nerve has also been shown to increase feeding (Rezek et al. 1975).”
Background
Gastric loads potentiate inhibition of food intake produced by a cholecystokinin analogue
Schwartz, G. J., Netterville, L. A., McHugh, P. R., & Moran, T. H. (1991) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1991.261.5.r1141 · Cited by 67
The role of mechanical forces and adenosine in the regulation of intestinal enterochromaffin cell serotonin secretion
Chin, A., Svejda, B., Gustafsson, B. I., Granlund, A. V. B., Sandvik, A. K., Timberlake, A. T., Sumpio, B. E., Pfragner, R., Modlin, I. M., & Kidd, M. S. (2011) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00087.2011 · Cited by 65 · cited 1×
“When mechanically stimulated, enterochromaffin cells release serotonin (Chin et al. 2012).”
Background
Physiology and morphology of neurons in the dorsal motor nucleus of the vagus and the nucleus of the solitary tract that are sensitive to distension of the small intestine
Zhang, X., Fogel, R., & Renehan, W. E. (1992) · The Journal of Comparative Neurology · doi:10.1002/cne.903230310 · Cited by 64 · cited 8×
“Using a combinatorial viral approach, Han et al. (2018) showed that terminals from the right nodose ganglion project to the ventromedial NTS, whereas those of the left nodose ganglion end in the AP.”
BackgroundInfluential
Costorage of enteroendocrine hormones evaluated at the cell and subcellular levels in male mice
Fothergill, L. J., Callaghan, B., Hunne, B., Bravo, D. M., & Furness, J. B. (2017) · Endocrinology · doi:10.1210/en.2017-00243 · Cited by 63
Glucagon-like peptide 1 and peptide YY are in separate storage organelles in enteroendocrine cells
Cho, H., Robinson, E. S., Rivera, L. R., McMillan, P. J., Testro, A., Nikfarjam, M., Bravo, D. M., & Furness, J. B. (2014) · Cell and Tissue Research · doi:10.1007/s00441-014-1886-9 · Cited by 62 · cited 1×
“At a subcellular level, these neuropeptides can be co-stored in single vesicles (Cho et al. 2014, Fothergill et al. 2017).”
Background
Vagotomy: Effect on Electrically Elicited Eating and Self-Stimulation in the Lateral Hypothalamus
Ball, G. G. (1974) · Science · doi:10.1126/science.184.4135.484 · Cited by 57 · cited 1×
“Phillips & Nikaido (1975) showed that stimulating the LH, a brain area involved in reward, induces voracious feeding, an effect that is abolished when the vagus nerve is severed (Ball 1974).”
Background
Regulation of ACTH secretory pathways in cultured pituitary cells
Schwartz, J., Gibson, S., & White, A. E. (1991) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1991.261.5.c793 · Cited by 57
Adenosine triphosphate is co-secreted with glucagon-like peptide-1 to modulate intestinal enterocytes and afferent neurons
Lu, V. B., Rievaj, J., O’Flaherty, E. A. A., Smith, C. A., Pais, R., Pattison, L. A., Tolhurst, G., Leiter, A. B., Bulmer, D. C., Gribble, F. M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09045-9 · Cited by 56 · cited 11×
“However, glucagonlike peptide 1 alone is not sufficient to elicit a vagal response; it requires the presence of ATP (Richards et al. 2014,Williams et al. 2016).”
BackgroundResultInfluential
Beiträge zur Kenntniss vom Bau der Geschmackswärzchen der Zunge
Lovén, C. (1868) · Archiv für Mikroskopische Anatomie · doi:10.1007/bf02955356 · Cited by 50 · cited 1×
“…tract contains specialized areas to sense ingested material was postulated by histologists as early as the 1860s. Schwalbe (1867) and Lovén (1868) observed a clustering of cells on the epithelial surface of the tongue, and Heidenhain (1870) extended these observations to the…”
Background
Glucose modulation of ATP-sensitive K-currents in wild-type, homozygous and heterozygous glucokinase knock-out mice
Sakura, H., Ashcroft, S. J. H., Terauchi, Y., Kadowaki, T., & Ashcroft, F. M. (1998) · Diabetologia · doi:10.1007/s001250050964 · Cited by 48 · cited 1×
“Depolarization then induces voltage-gated Ca channels to open, triggering vesicle fusion and release (Sakura et al. 1998).”
Background
Impulses in Vagal Afferent Fibres from Stretch Receptors in the Stomach and their Role in the Peripheral Mechanism of Hunger
PAINTAL, A. S. (1953) · Nature · doi:10.1038/1721194a0 · Cited by 46 · cited 1×
“Paintal (1953) performed electrophysiological experiments in cats and determined that most of the vagal terminals of the stomach end primarily in stretch mechanoreceptors.”
Background
Regulation of intracellular pH by cultured opossum kidney cells
Montrose, M. H., & Murer, H. (1990) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1990.259.1.c110 · Cited by 46
On the innervation of the ileal mucosa in the rat‐a synapse
Newson, B., Ahlman, H. K., Dahlström, A., Gupta, T. K. D., & Nyhus, L. M. (1979) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1979.tb06357.x · Cited by 44 · cited 1×
“The second report did not have the resolution to state definitively that there was a synapse, and the authors therefore merely suspected that it was a synapse (Newson et al. 1979).”
Background
Das Epithel der Papillae vallatae
Schwalbe, G. (1867) · Archiv für Mikroskopische Anatomie · doi:10.1007/bf02960479 · Cited by 41
Loss of the TGFβ-Activating Integrin αvβ8 on Dendritic Cells Protects Mice from Chronic Intestinal Parasitic Infection via Control of Type 2 Immunity
Worthington, J. J., Klementowicz, J. E., Rahman, S., Czajkowska, B. I., Smedley, C., Waldmann, H., Sparwasser, T. D., Grencis, R. K., & Travis, M. A. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003675 · Cited by 40 · cited 1×
“Helminth infections, such as Trichinella spiralis, lead to hypophagia, which depends on the presence and number of enteroendocrine cells (Worthington et al. 2013).”
Background
Foreign anions modulate volume set point of sheep erythrocyte K-Cl cotransport
Lauf, P. K. (1991) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1991.260.3.c503 · Cited by 36
Dietary Lipids Inform the Gut and Brain about Meal Arrival via CD36-Mediated Signal Transduction
Sundaresan, S., & Abumrad, N. A. (2015) · Journal of Nutrition · doi:10.3945/jn.115.215483 · Cited by 35 · cited 1×
“In taste receptor cells, fat translocation through CD36 activates a phospholipase Cβ pathway to mediate intracellular Ca signaling (Sundaresan & Abumrad 2015).”
Background
Amino acid sensing by enteroendocrine STC-1 cells: role of the Na+-coupled neutral amino acid transporter 2
Young, S. H., Rey, O., Sternini, C., & Rozengurt, E. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00518.2009 · Cited by 35 · cited 1×
“SNAT2 is a neutral l-amino acid transporter that requires the cotransport of Na+ to elicit Ca activity in the enteroendocrine cell line (STC-1 cells) (Young et al. 2010).”
Background
Decreased Weight Gain and Food Intake in Vagotomized Rats
Mordes, J. P., Herrera, M. G., & Silen, W. (1977) · Experimental Biology and Medicine · doi:10.3181/00379727-156-39917 · Cited by 31 · cited 1×
“Vagotomized rats were reported to have decreased food intake (Mordes et al. 1977).”
Background
Human enteroendocrine cell responses to infection with Chlamydia trachomatis: a microarray study
Dlugosz, A., Muschiol, S., Zakikhany, K., Assadi, G., D’Amato, M., & Lindberg, G. (2014) · Gut Pathogens · doi:10.1186/1757-4749-6-24 · Cited by 25 · cited 1×
“Chlamydia trachomatics, for example, directly infects human enteroendocrine cells (Dlugosz et al. 2011).”
Background
The survival of vagal and glossopharyngeal sensory neurons is dependent upon dystonin
Ichikawa, H., Repentigny, Y. D., Kothary, R., & Sugimoto, T. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.08.081 · Cited by 14 · cited 1×
“The nodose ganglia of the mouse contain approximately 2,300 neurons (Ichikawa et al. 2006).”
Background
Infection of human enteroendocrine cells with Chlamydia trachomatis: a possible model for pathogenesis in irritable bowel syndrome
Dlugosz, A., Zakikhany, K., Muschiol, S., Hultenby, K. R., & Lindberg, G. (2011) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2011.01765.x · Cited by 6 · cited 1×
“Chlamydia trachomatics, for example, directly infects human enteroendocrine cells (Dlugosz et al. 2011).”
Background

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Sorted by citations

Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders
Chen, Y., Xu, J., & Chen, Y. (2021) · Nutrients · doi:10.3390/nu13062099 · Cited by 917
“It was previously believed that the sensory information from the gut could only be transmitted to the brain via the release of hormones by enteroendocrine cells [30].”
Background
Neural circuits of interoception
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Authors: Kaelberer, M. M., Rupprecht, L. E., Liu, W. W., Weng, P., & Bohórquez, D. V.
Affiliations: Duke University (US)
Corresponding author: Bohórquez, Diego V.
ORCID: Kaelberer, Melanie Maya
Rupprecht, Laura E.
Liu, Winston W.
Bohórquez, Diego V.
Venue: Annual Review of Neuroscience
Publisher: Annual Reviews
Published: 2020-07-08
Volume: 43
Issue: 1
Pages: 337-353
ISSN: 0147-006X (ISSN-L)
1545-4126
DOI: 10.1146/annurev-neuro-091619-022657
PMC: PMC7573801
OpenAlex: W3007159566
Cited by: 236
References: 115
Citations by year: 2026: 44 · 2025: 58 · 2024: 43 · 2023: 36 · 2022: 26 · 2021: 22 · 2020: 7
FWCI: 3.99
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Annual Review of Neuroscience (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Duke-NUS Medical School
National Institutes of Health (5r21at010818-02)
National Institute of Mental Health (DP2MH122402)
National Institute of General Medical Sciences (T32GM007171)
National Center for Complementary and Integrative Health (R21-AT010818)
Topics: Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
Keywords: enteroendocrine cells, synapses, neurotransmission, vagus nerve, intestinal hormones
MeSH terms: Animals, Brain, Humans, Neurons, Synapses, Vagus Nerve, Signal Transduction, Enteroendocrine Cells

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

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