Abstract

It is likely that the enteric nervous system responds in a paracrine fashion to intraluminal stimulation by release of 5-HT by mucosal EC cells. Intrinsic and extrinsic sensory nerves express 5-HT1P/4 and 5-HT3 receptor respectively. Intestinal epithilial cells express a plasmalemmal 5HT transporter (SERT) similar to that of serotoninergic neurons, which controls the extent to which 5-HT acts as a mucosal signaling molecule. In this proposal mice lacking SERT will be used to 1. determine what compensatory changes occur in the gut of SERT- mice 2. Determine what changes in GI motility and central signaling occur in these mice and 3. Investigate additional intraluminal stimuli that can activate submucosal primary afferent neurons other than pressure distortion in guinea pig, SERT - and control mice. A combination of immunocytochemical, molecular and electrophysiological techniques will be used to address these aims. The SERT - mice model provides a hyperserotonergic model of the gut, which may represent states of disease such as IBS, infection, use of antidepressants etc.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS012969-27
Application #
6529391
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Mitler, Merrill
Project Start
1977-12-01
Project End
2004-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
27
Fiscal Year
2002
Total Cost
$341,000
Indirect Cost

  Institution

Name
Columbia University (N.Y.)
Department
Pathology
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032

  Publications

Smith, Terence K; Gershon, Michael D (2015) CrossTalk proposal: 5-HT is necessary for peristalsis. J Physiol 593:3225-7
Welch, Martha G; Margolis, Kara G; Li, Zhishan et al. (2014) Oxytocin regulates gastrointestinal motility, inflammation, macromolecular permeability, and mucosal maintenance in mice. Am J Physiol Gastrointest Liver Physiol 307:G848-62
Westphalen, C Benedikt; Asfaha, Samuel; Hayakawa, Yoku et al. (2014) Long-lived intestinal tuft cells serve as colon cancer-initiating cells. J Clin Invest 124:1283-95
Gan, Lin; Wang, Mingli; Chen, Jason J et al. (2014) Infected peripheral blood mononuclear cells transmit latent varicella zoster virus infection to the guinea pig enteric nervous system. J Neurovirol 20:442-56
Margolis, Kara Gross; Stevanovic, Korey; Li, Zhishan et al. (2014) Pharmacological reduction of mucosal but not neuronal serotonin opposes inflammation in mouse intestine. Gut 63:928-37
Heredia, Dante J; Gershon, Michael D; Koh, Sang Don et al. (2013) Important role of mucosal serotonin in colonic propulsion and peristaltic reflexes: in vitro analyses in mice lacking tryptophan hydroxylase 1. J Physiol 591:5939-57
Gershon, Michael D (2013) 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr Opin Endocrinol Diabetes Obes 20:14-21
Goldberg, David; Borojevic, Rajka; Anderson, Monique et al. (2013) Slit/Robo-mediated chemorepulsion of vagal sensory axons in the fetal gut. Dev Dyn 242:9-15
Gershon, Michael D (2012) Serotonin is a sword and a shield of the bowel: serotonin plays offense and defense. Trans Am Clin Climatol Assoc 123:268-80; discussion 280
Gross, Erica R; Gershon, Michael D; Margolis, Kara G et al. (2012) Neuronal serotonin regulates growth of the intestinal mucosa in mice. Gastroenterology 143:408-17.e2

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