Altered neuronal density and neurotransmitter expression in the ganglionated region of Ednrb null mice

Implications for Hirschsprung's disease

I. Zaitoun, C. S. Erickson, A. J. Barlow, T. R. Klein, A. F. Heneghan, Joseph Pierre, M. L. Epstein, Ankush Gosain

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalNeurogastroenterology and Motility
Volume25
Issue number3
DOIs
StatePublished - Mar 1 2013

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Hirschsprung Disease
Neurotransmitter Agents
Ganglia
Colon
Choline O-Acetyltransferase
Neural Crest
Neurons
Constipation
Substance P
Ileum
Genotype

All Science Journal Classification (ASJC) codes

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

Cite this

Altered neuronal density and neurotransmitter expression in the ganglionated region of Ednrb null mice : Implications for Hirschsprung's disease. / Zaitoun, I.; Erickson, C. S.; Barlow, A. J.; Klein, T. R.; Heneghan, A. F.; Pierre, Joseph; Epstein, M. L.; Gosain, Ankush.

In: Neurogastroenterology and Motility, Vol. 25, No. 3, 01.03.2013.

Research output: Contribution to journalArticle

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abstract = "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.",
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