Anatomy and Neuroscience - Research Publications

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Author: Stamp, Lincon × Author: Young, Heather × End date: 2015 × Start date: 2015 ×

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    Surgical Intervention to Rescue Hirschsprung Disease in a Rat Model
    Stamp, LA ; Obermayr, F ; Pontell, L ; Young, HM ; Xie, D ; Croaker, DH ; Song, Z-M ; Furness, JB (KOREAN SOC NEUROGASTROENTEROLOGY & MOTILITY, 2015-10)
    BACKGROUND/AIMS: Rats with a spontaneous null mutation in endothelin receptor type B or Ednrb (sl/sl; spotting lethal) lack enteric neurons in the distal bowel and usually die within the first week after birth. This early postnatal lethality limits their use for examining the potential of cell therapy to treat Hirschsprung disease, and for studies of the influence of EDNRB on the mature CNS and vascular systems. METHODS: We have developed a surgical intervention to prolong the life of the spotting lethal sl/sl rat, in which we perform a colostomy on postnatal (P) day 4-6 rats to avoid the fatal obstruction caused by the lack of colonic enteric neurons. RESULTS: The stomas remained patent and functional and the rats matured normally following surgery. Weight gains were comparable between control and Hirschsprung phenotype (sl/sl) rats, which were followed until 4 weeks after surgery (5 weeks old). We confirmed the absence of enteric neurons in the distal colon of rats whose lives were saved by the surgical intervention. CONCLUSIONS: This study provides a novel approach for studying EDNRB signalling in multiple organ systems in mature rats, including an animal model to study the efficacy of cell therapy to treat Hirschsprung disease.
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    Ion Channel Expression in the Developing Enteric Nervous System
    Hirst, CS ; Foong, JPP ; Stamp, LA ; Fegan, E ; Dent, S ; Cooper, EC ; Lomax, AE ; Anderson, CR ; Bornstein, JC ; Young, HM ; McKeown, SJ ; Schubert, M (PUBLIC LIBRARY SCIENCE, 2015-03-23)
    The enteric nervous system arises from neural crest-derived cells (ENCCs) that migrate caudally along the embryonic gut. The expression of ion channels by ENCCs in embryonic mice was investigated using a PCR-based array, RT-PCR and immunohistochemistry. Many ion channels, including chloride, calcium, potassium and sodium channels were already expressed by ENCCs at E11.5. There was an increase in the expression of numerous ion channel genes between E11.5 and E14.5, which coincides with ENCC migration and the first extension of neurites by enteric neurons. Previous studies have shown that a variety of ion channels regulates neurite extension and migration of many cell types. Pharmacological inhibition of a range of chloride or calcium channels had no effect on ENCC migration in cultured explants or neuritogenesis in vitro. The non-selective potassium channel inhibitors, TEA and 4-AP, retarded ENCC migration and neuritogenesis, but only at concentrations that also resulted in cell death. In summary, a large range of ion channels is expressed while ENCCs are colonizing the gut, but we found no evidence that ENCC migration or neuritogenesis requires chloride, calcium or potassium channel activity. Many of the ion channels are likely to be involved in the development of electrical excitability of enteric neurons.