Altered neuronal density and neurotransmitter expression in the ganglionated region ofEdnrbnull mice: implications for Hirschsprung's disease

Autor:	Taylor R. Klein, Miles L. Epstein, Aaron F. Heneghan, Ankush Gosain, Joseph F. Pierre, Amanda J. Barlow, Christopher S. Erickson, Ismail Zaitoun
Rok vydání:	2013
Předmět:	medicine.medical_specialty Colon Physiology Substance P Ileum Biology Enteric Nervous System Article Mice chemistry.chemical_compound Internal medicine medicine Animals Hirschsprung Disease Receptor Neurotransmitter Hirschsprung's disease Mice Knockout Neurons Neurotransmitter Agents Endocrine and Autonomic Systems Gastroenterology Neural crest medicine.disease Immunohistochemistry Receptor Endothelin B Choline acetyltransferase Disease Models Animal Endocrinology medicine.anatomical_structure nervous system chemistry Enteric nervous system
Zdroj:	Neurogastroenterology & Motility. 25:e233-e244
ISSN:	1350-1925
DOI:	10.1111/nmo.12083
Popis:	Background Hirschsprung's disease (HSCR) is a congenital condition in which enteric ganglia, formed from neural crest cells (NCC), are absent from the terminal bowel. Dysmotility and constipation are common features of HSCR that persist following surgical intervention. This persistence suggests that the portion of the colon that remains postoperatively is not able to support normal bowel function. To elucidate the defects that underlie this condition, we utilized a murine model of HSCR. Methods Mice with NCC-specific deletion of Ednrb were used to measure the neuronal density and neurotransmitter expression in ganglia. Key Results At the site located proximal to the aganglionic region of P21 Ednrb null mice, the neuronal density is significantly decreased and the expression of neurotransmitters is altered compared with het animals. The ganglia in this colonic region are smaller and more isolated while the size of neuronal cell bodies is increased. The percentage of neurons expressing neuronal nNOS and VIP is significantly increased in Ednrb nulls. Conversely, the percentage of choline acetyltransferase (ChAT) expressing neurons is decreased, while Substance P is unchanged between the two genotypes. These changes are limited to the colon and are not detected in the ileum. Conclusions & Inferences We demonstrate changes in neuronal density and alterations in the balance of expression of neurotransmitters in the colon proximal to the aganglionic region in Ednrb null mice. The reduced neuronal density and complementary changes in nNOS and ChAT expression may account for the dysmotility seen in HSCR.
Databáze:	OpenAIRE
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