Research Mentor(s): Amy Rumora, Postdoctoral Fellow
Research Mentor School/College/Department: Neurology, Michigan Medicine
Presentation Date: Thursday, April 22, 2021
Session: Session 2 (11am – 11:50am)
Breakout Room: Room 12
Diabetes is a global epidemic that affects 463 million individuals. Approximately 50% of diabetic patients develop a serious complication called diabetic neuropathy (DN) that can also develop in patients with pre-diabetes and obesity. DN is characterized by tingling or burning, sharp pains, and eventual loss of sensation in the hands or feet that results from significant nerve damage. Despite the severity of DN, there are no disease-modifying treatments for DN associated with type 2 diabetes, prediabetes, or obesity. Recent studies indicate that dyslipidemia correlates with DN, suggesting that fatty acids may contribute to DN onset or progression. Dorsal root ganglion (DRG) neurons are a cluster of primary sensory neurons located just outside the spinal cord that extend axons into the nerves and transmit sensory information from the peripheral nervous system to the central nervous system. DRG neurons depend on mitochondrial trafficking and function to produce ATP in the axons, and it has been reported that insulin signaling regulates mitochondrial function. In this study, we sought to determine whether the presence of the insulin receptor regulates axonal mitochondrial trafficking in fatty acid-treated DRG neurons. DRG neurons from insulin receptor knockout mice (IRKO) were given six different treatments to explore the effect of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) on axonal mitochondrial trafficking. A kymographing analysis was used to analyze mitochondrial transport in individual DRG axons and identify the percent of mitochondria that were stationary or motile. Interestingly, we found significantly fewer motile mitochondria in the IRKO DRG axons compared to wild type DRG axons. The SFA treatments impaired mitochondrial trafficking, while the addition of MUFAs prevented the reduction in mitochondrial trafficking in both wild type and IRKO DRG neurons. This study suggests that the loss of the insulin receptor reduces basal mitochondrial trafficking in DRG neurons but does not contribute to fatty acid-induced alterations in mitochondrial trafficking.