Diagnostic Tool for Diabetic Neuropathy: Investigation of Mitochondrial Dynamics of Intraepidermal Nerve Fibers in Diabetic Mice
Robell, Nicholas J.
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Diabetic neuropathy is a common complication of diabetes involving the length dependent degeneration of sensory nerves in the body resulting in sensory loss. The underlying hyperglycemia associated with diabetes can cause changes in mitochondrial dynamics in dorsal root ganglia cells prior to neuronal death. It is hypothesized that the clumping of mitochondria may precede the development of diabetic neuropathy. Currently, no tool is available to measure mitochondrial dynamics in sensory nerves. The goal of this study was to develop a diagnostic tool to measure mitochondrial dynamics in intraepidermal nerves and assess the progression of diabetic neuropathy. A mouse model of Type 2 diabetes was used to study changes in mitochondrial dynamics within sensory nerves during the progression of diabetes and diabetic neuropathy. Three-dimensional images of fluorescently tagged markers for nerve and mitochondria were generated using confocal microscopy. A protocol was developed to analyze and quantify mitochondria dynamics with 3D analysis software. These mitochondrial dynamic data suggest that mitochondria clumps occur in sensory nerves prior to the development of diabetic neuropathy. The mitochondrial clumping may present a significant event in diabetic neuropathy and may provide a useful biomarker for the disease. The protocol developed in this experiment can be implemented in future studies of mitochondrial dynamics as well. This tool would be applicable to other models of diabetic neuropathy and after refining may provide a clinical measure for early detection of diabetic neuropathy.
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