Iron-mediated redox modulation in neural plasticity

Abstract

The role of iron in brain physiology has focused on the neuropathological, effects due to iron-induced oxidative stress. However, our recent work has established a physiological relationship between the iron-mediated oxidative modification and normal neuronal function. Our results obtained from hippocampal neurons, suggest that iron-generated reactive species oxygen (ROS) are involved in calcium signaling initiated by stimulation of NMDA receptors. This signal is amplified by ryanodine receptors (RyR), a redox- sensitive calcium channel, allowing the phosphorylation and nuclear translocation of ERK1/2. Furthermore, using electrophysiological approaches, we showed that iron is required for basal synaptic transmission and full expression of long-term potentiation, a type of synaptic plasticity. Our data combined suggest that the oxidative effect of iron is critical to activate processes that are downstream of NMDAR activation. Finally, due to the high reactivity of DNA with iron-generated ROS, we hypothesize an additional function of iron in gene regulation.