Review paper

Freeman, Andrew; Cunningham, Katharine; Tyers, M.B.

doi:10.1097/00001813-199204000-00001

Cited by 67 publications

(3 citation statements)

References 0 publications

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“…Furthermore, different enterochromaffin cell subtypes can have different effects on gut motility, suggesting at least partially nonoverlapping communication pathways with downstream neurons. These findings are consistent with a role for enterochromaffin cells in toxin-induced illness responses, and interestingly, pharmacological blockade of the serotonin receptor HTR3A is a clinical mainstay for nausea treatment ( Freeman et al, 1992 ). Other enteroendocrine cell types, including those that produce CCK, GIP, GLP1, neurotensin, and somatostatin, express nutrient receptors yet elicit different physiological and behavioral responses.…”

Section: Resultssupporting

confidence: 77%

Enteroendocrine cell lineages that differentially control feeding and gut motility

Hayashi

Kaye

Douglas

et al. 2023

eLife

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Enteroendocrine cells are specialized sensory cells of the gut-brain axis that are sparsely distributed along the intestinal epithelium. The functions of enteroendocrine cells have classically been inferred by the gut hormones they release. However, individual enteroendocrine cells typically produce multiple, sometimes apparently opposing, gut hormones in combination, and some gut hormones are also produced elsewhere in the body. Here, we developed approaches involving intersectional genetics to enable selective access to enteroendocrine cells in vivo in mice. We targeted FlpO expression to the endogenous Villin1 locus (in Vil1-p2a-FlpO knock-in mice) to restrict reporter expression to intestinal epithelium. Combined use of Cre and Flp alleles effectively targeted major transcriptome-defined enteroendocrine cell lineages that produce serotonin, glucagon-like peptide 1, cholecystokinin, somatostatin, or glucose-dependent insulinotropic polypeptide. Chemogenetic activation of different enteroendocrine cell types variably impacted feeding behavior and gut motility. Defining the physiological roles of different enteroendocrine cell types provides an essential framework for understanding sensory biology of the intestine.

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Section: Resultssupporting

confidence: 77%

Enteroendocrine cell lineages that differentially control feeding and gut motility

Hayashi

Kaye

Douglas

et al. 2023

eLife

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show abstract

“…In this way, gut and respiratory sensory neurons could potentially engage different neural circuits that lead, for example, to either cough or nausea 31 , 49 . Consistent with this notion, various routes to sickness are differentially sensitive to pharmacological inhibition; for example, gut malaise is treated clinically using antagonists of the serotonin receptor HTR3A 50 . Understanding the diversity of sensory pathways to sickness and when they are engaged by different pathogen infections will provide an essential framework for deciphering this complex and poorly understood physiological state, and may enable improved therapeutic interventions.…”

Section: Discussionmentioning

confidence: 96%

An airway-to-brain sensory pathway mediates influenza-induced sickness

Bin

Prescott

Horio

et al. 2023

Nature

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Pathogen infection causes a stereotyped state of sickness that involves neuronally orchestrated behavioural and physiological changes1,2. On infection, immune cells release a ‘storm’ of cytokines and other mediators, many of which are detected by neurons3,4; yet, the responding neural circuits and neuro–immune interaction mechanisms that evoke sickness behaviour during naturalistic infections remain unclear. Over-the-counter medications such as aspirin and ibuprofen are widely used to alleviate sickness and act by blocking prostaglandin E2 (PGE2) synthesis5. A leading model is that PGE2 crosses the blood–brain barrier and directly engages hypothalamic neurons2. Here, using genetic tools that broadly cover a peripheral sensory neuron atlas, we instead identified a small population of PGE2-detecting glossopharyngeal sensory neurons (petrosal GABRA1 neurons) that are essential for influenza-induced sickness behaviour in mice. Ablating petrosal GABRA1 neurons or targeted knockout of PGE2 receptor 3 (EP3) in these neurons eliminates influenza-induced decreases in food intake, water intake and mobility during early-stage infection and improves survival. Genetically guided anatomical mapping revealed that petrosal GABRA1 neurons project to mucosal regions of the nasopharynx with increased expression of cyclooxygenase-2 after infection, and also display a specific axonal targeting pattern in the brainstem. Together, these findings reveal a primary airway-to-brain sensory pathway that detects locally produced prostaglandins and mediates systemic sickness responses to respiratory virus infection.

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“…The importance of peripheral 5-HT 3 receptors and vagal afferent fibers in anticancer induced emesis points to a primary peripheral site of action, 134,135 although a part central mechanism by blockade of 5-HT 3 receptors in the area postrema and/or the nucleus tractus solitarius cannot be entirely ruled out. 136,137 It is believed that 5-HT is released by radiation and chemotherapy from enterochromaffin cells in the gut mucosa 138 which stimulates vagal afferent nerves supplying the upper gut, resulting in emesis. 139 In cancer therapy, many comparator studies have been performed, both alone and in combination with adjunct agents such as dexamethasone with which synergy increases the response rate.…”

Section: A Anti-emesis 130mentioning

confidence: 99%