"The Enteric Nervous System in gut and brain disorders"
Abstract
The UMR TENS proposes different experimental approaches to evaluate the permeability and the intestinal motricity in vivo and ex vivo. It also has tools to study animal behavior through the gut-brain axis.
To know: All research projects requiring animal experiments are submitted in advance to the Ministry of Higher Education and Research and to the ethics committee for validation.
Intestinal permeability:
intestinal permeability is characterized in vivo in small animals using permeability markers. These markers are administered orally, then cross the intestinal barrier and enter the bloodstream. A blood sample is then taken to measure these markers and thus assess intestinal permeability globally.
In order to study the permeability ex vivo in a precise portion of the intestine (jejunum, ileum, colon), our unit has Ussing chambers. This device allows to artificially recreate 2 compartments: one compartment corresponding to the lumen of the digestive tract and one compartment corresponding to the bloodstream. The permeability of the intestinal mucosa is evaluated by measuring the passage of "markers" from the lumen of the tube to the bloodstream, through the intestinal fragment.
Intestinal motricity:
Intestinal motility can be characterized in vivo by various techniques. Total transit time is assessed by administering a (non-absorbable) dye and measuring the time elapsed between administration and emission of a stained stool. Colonic transit is assessed by measuring the frequency of stool output. The distal colonic transit is characterized by measuring the time elapsed between the insertion of a small glass bead and its expulsion.
In order to study the ex vivo motricity in a precise portion of the intestine (jejunum, ileum, colon), our unit has motricity chambers coupled to an acquisition and stimulation system. This device allows us to characterize the contractile activity of segments of the digestive tract, which depends on two components: the ENS and the smooth muscle fibers that it innervates. The use of electrical stimulations in combination with different pharmacological agents allows to characterize on the one hand the response of the SNE to a stimulation, and on the other hand the response of the smooth muscle fibres.
Animal behavior:
"Open field" test:
Study of general activity - exploratory behavior - stereotypy
"Elevated Cross Maze" test:
Anxiety Study
"Rotarod" test:
Study of motor activity
"3-Arm Maze" test:
Memory Study
3-chamber social interaction test
Funding
Publications
Aubert P, Guinobert I, Blondeau C, Bardot V, Ripoche I, Chalard P, Neunlist M. Basal and Spasmolytic Effects of a Hydroethanolic Leaf Extract of Melissa officinalis L. on Intestinal Motility: An Ex Vivo Study. J Med Food. 2019 Jul;22(7):653-662. PMID:30990736 Link
Aubert P, Oleynikova E, Rizvi H, Ndjim M, Le Berre-Scoul C, Grohard PA, Chevalier J, Segain JP, Le Drean G,Neunlist M, Boudin H. Maternal protein restriction induces gastrointestinal dysfunction and enteric nervous system remodeling in rat offspring. FASEB J. 2018 Aug 1 PMID: 30067379. Link
Workman MJ, Mahe MM, Trisno S, Poling HM, Watson CL, Sundaram N, Chang CF, Schiesser J, Aubert P, Stanley EG, Elefanty AG, Miyaoka Y, Mandegar MA, Conklin BR, Neunlist M, Brugmann SA, Helmrath MA, Wells JM. Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system. Nat Med. 2016 Nov 21. doi: 10.1038/nm.4233. PMID: 27869805. Link
Vanhaecke T, Aubert P, Grohard PA, Durand T, Hulin P, Paul-Gilloteaux P, Ligneul A, Naveilhan P, Boudin H, Fressange-Mazda C, Le Ruyet P, Neunlist M. L. fermentum CECT 5716 prevents stress-induced intestinal barrier dysfunctions in newborn rats. Neurogastroenterol Motil. 2017 Aug;29(8). PubMed PMID: 28370715 Link
Brégeon J, Coron E, Da Silva AC, Jaulin J, Aubert P, Chevalier J, Vergnolle N, Meurette G, Neunlist M. Sacral nerve stimulation enhances early intestinal mucosal repair following mucosal injury in a pig model. J Physiol. 2016 Aug 1;594 (15):4309-23. Link
Provost M, Brégeon J, Aubert P, Duchalais-Dassonneville E, D'Aldebert E, Vergnolle N, Neunlist M, Meurette G. Effects of 1-week sacral nerve stimulation on the rectal intestinal epithelial barrier and neuromuscular transmission in a porcine model. Neurogastroenterol Motil. 2015 Jan;27(1):40-50. Link
Meurette G, Blanchard C, Duchalais-Dassonneville E, Coquenlorge S, Aubert P, Wong M, Lehur PA, Neunlist M. Sacral nerve stimulation enhances epithelial barrier of the rectum: results from a porcine model. Neurogastroenterol Motil. 2012 Mar;24(3):267-e110 Link