The effects of glucagon-like peptide 2 on enteric neurons in intestinal inflammation.
BACKGROUND
Intestinal inflammation alters the structure and function of the enteric nervous system (ENS). Glucagon-like peptide 2 (GLP-2) reduces intestinal inflammation and has trophic effects on isolated neurons. This study examined the effects of GLP-2 treatment on the submucosal plexus of rat colon in the trinitrobenzene sulfonic acid (TNBS) model of colitis.


METHODS
After administration of TNBS or saline/ethanol for controls, animals were allocated to treatment with GLP-2 (50 μg kg⁻¹ day⁻¹, s.c.) or sham injection of vehicle, twice daily. Animals were monitored, following clinical parameters, and killed on day 5. The number of neuronal cell bodies per ganglion was quantified using immunohistochemistry on submucosal whole mount preparations, with further characterization of specific subpopulations using antibodies against vasoactive intestinal polypeptide (VIP), neuronal nitric oxide synthase (nNOS), and enteric glial cells with glial fibrillary acid protein and S100.


RESULTS
Glucagon-like peptide 2 treatment was associated with a significant amelioration of weight loss, and reduced neutrophil infiltration and microscopic colitis scores in the TNBS animals. Inflammation resulted in a loss of enteric neurons in submucosal ganglia; GLP-2 treatment restored the enteric neuronal populations to normal. In control, non-inflamed animals, GLP-2 treatment increased the number of VIP expressing neurons per ganglion; in TNBS-treated animals, GLP-2 prevented an inflammation-induced reduction in the numbers of VIP expressing neurons per ganglion. Glucagon-like peptide 2 did not change the numbers of nNOS neurons or enteric glial cells in either the control, or inflamed state.


CONCLUSIONS
These findings show that GLP-2 increased the number of VIP expressing neurons in normal animals, and prevents the inflammation-induced loss of neurons in the colonic submucosal ganglia, with an increase in the proportion of VIP expressing neurons. They suggest that GLP-2 may have a role in protecting or regulating the circuitry of the ENS under basal and inflamed states.
Sigalet
D L
DL
Department of Surgery, Faculty of Medicine, Snyder Institute of Infection, Immunity & Inflammation, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada. sigalet@ucalgary.ca
Wallace
L
L
De Heuval
E
E
Sharkey
K A
KA
D000818:Animals; D003106:Colon / Q000294:innervation* / Q000473:pathology*; D017615:Enteric Nervous System / Q000166:cytology* / Q000187:drug effects*; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology*; D006801:Humans; D007422:Intestines / Q000473:pathology*; D008297:Male; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D053767:Glucagon-Like Peptide 2