Grant: CIHR Fellowship

Worldwide, cases of type 1 and 2 diabetes are reaching epidemic numbers. Diabetes is associated with nerve complications known as diabetic peripheral neuropathy, also known as DPN. DPN affects approximately 30% of individuals with diabetes. Symptoms include incapacitating pain, loss of certain sensations, foot ulceration, infection and amputation. No effective treatment currently exists to reverse or even slow the progression of DPN. We have recently shown that mitochondria, the powerhouse of cells, have reduced function in neurons from diabetic rodent models. This is significant as the neuron requires substantial amounts of energy to fuel its processes. In this proposal, we aim to study the role of a specific protein, PGC-1alpha. PGC-1alpha has been shown to regulate both the number of mitochondria within a cell as well as their function. The level of PGC-1alpha protein is lower in neurons from diabetic models. Firstly, we aim to understand how the expression of PGC-1alpha protein is regulated in diabetic neurons. Secondly, we propose to induce diabetes in our rodent model and enhance PGC-1alpha activity following the development of neuropathy. If increased PGC-1alpha activity restores mitochondrial function and this improves or reverses the diabetes-induced neuropathy, we will have shown the importance of maintaining mitochondria health in neurons in diabetic individuals. If a positive link between PGC-1alpha and diabetic neuropathy is found, these studies could lead to potential targets for therapeutic avenues in diabetic neuropathy. In addition, these findings could be extended to a number of neurodegenerative diseases that share common pathological features with diabetic neuropathy, such as Alzheimer's disease.