Neurite growth induced by red light-caused intracellular reactive oxygen species production through cytochrome c oxidase activation

The applications of red-light photobiomodulation (PBM) to enhance neurite growth have been proposed for many years. However, the detailed mechanisms require further studies. In the present work we used a focused red-light spot to illuminate the junction of the longest neurite and the soma of a neuroblastoma cell (N2a), and demonstrated enhanced neurite growth at 620 nm and 760 nm with adequate illumination energy fluences. In contrast, 680 nm light showed no effect on neurite growth. The neurite growth was accompanied with the increase of intracellular reactive oxygen species (ROS). Using Trolox to reduce the ROS level, this red light-induced neurite growth was hindered. Suppressing the activities of cytochrome c oxidase (CCO) by using either a small-molecule inhibitor or siRNA abrogated the red light-induced neurite growth. These results suggest that red light-induced ROS production through the activation of CCO could be beneficial for neurite growth.