Involvement of ROS signal in aging and regulation of brain functions.

Reactive oxygen species (ROS) are redox-signaling molecules involved in aging and lifestyle-related diseases. In the brain, in addition to the production of ROS as byproducts of metabolism, expression of ROS synthases has recently been demonstrated, suggesting possible involvement of ROS in various brain functions. This review highlights current knowledge on the relationship between ROS and brain functions, including their contribution to age-related decline in synaptic plasticity and cognitive function. While most studies demonstrate either the positive or negative effects of ROS on synaptic plasticity, the dual effects of ROS at individual synapses have been demonstrated recently in the mouse cerebellum. Furthermore, the cooperative interaction between these two effects determines the direction of synaptic plasticity. It is anticipated that further elucidation of both the positive and negative effects of ROS on brain function will lead to the development of more effective therapeutic strategies with fewer side effects for ROS-related brain dysfunction.