Grant: Master's Award: Canada Graduate Scholarships

Inflammatory bowel diseases (IBD; eg, Crohn's Disease) are chronically debilitating conditions that burden both the diseased individual and the health-care system. The cause of IBD is not known and it is difficult to develop effective therapeutic treatments, but the effect of inflammation on the intestine can be studied using animal models. This has shown the presence of damage to many types of cells, including the death of neurons that comprises the enteric nervous system (ENS). Outside the intestine, proteins called neurotrophins promote survival and repair of neurons and we recently found that a protein called glial-derived neurotrophic factor (GDNF) is important for enteric neuron survival in the new born animal. Now, we ask whether GDNF can aid in survival in the adult ENS during inflammation. Specifically, we propose that GDNF level rise in inflammation, and help to limit the damage to the neurons. We will look at the effect of inflammation on production of GDNF by intestinal smooth muscle cells (ISMC) using a tissue culture model. In this, ISMC are studied outside the body and their ability to make GDNF and support neurons can be measured. Then, we will use available technology to cause ISMC to make greatly increased levels of GDNF in the live animal and see if this improves the outcome of inflammation, hoping to see a reduction in the death of neurons. The ENS is critical for regulation of many intestinal functions, from contraction and relaxation to the absorption of nutrients. These processes are disturbed in inflammation, leading to the unpleasant symptoms associated with IBD, and if the neurons are lost, there is slow or absent recovery of control. Thus, preservation of neurons in the face of an inflammatory challenge may help alleviate some of these symptoms, and may be beneficial to individuals suffering from chronic inflammatory episodes.