Mitochondrial hydrogen peroxide levels in healthy peripheral nerves and peripheral neuropathies

Abstract

Mitochondria within neuronal axons of peripheral nerves are important for healthy neuronal function. Mitochondria have a multitude of functions in axons, but one major function is probably to produce ATP in order to maintain the Na/K ATPase activity, which is required for repeated conduction of action potentials. Especially nodes of Ranvier, non-myelinated areas where action potentials are regenerated, have a high energy demand. Not only ATP, but also reactive oxygen species (ROS) are produced in the process of ATP synthesis and although ROS can cause damage to the cell, they also play an important role in cell signaling. By using viral vectors expressing a fluorescent probe to detect H2O2 in mitochondria, we are able to observe changes in ROS production by axonal mitochondria as a response to physiological or neuropathic stimuli in vivo. By inducing action potentials via electrical stimulation, we observed that the level of H2O2 in axonal mitochondria can either increase or decrease, depending on the pattern of nerve firing. Moreover, we observed that the level of H2O2 in axonal mitochondria increases when the axon becomes demyelinated, but the production of H2O2 returns to healthy levels once remyelination occurs.