Since the late 1990s, a number of studies from our laboratory have indicated that reactive oxygen species (ROS), such as superoxide and hydrogen peroxide (H2O2), are important signaling molecules underlying hippocampal LTP and memory. Our findings are in contrast to the commonly held notion that ROS are exclusively destructive molecules that hinder neuronal and cognitive function during degenerative processes underlying Alzheimer’s and Parkinson’s diseases, as well as normal aging. We have shown that ROS are required for normal hippocampal function at the molecular, cellular, behavioral levels. Specifically, we have found that ROS are required for the full expression of hippocampal LTP and memory, as well as several signal transduction cascades that are underlie LTP and memory. We currently are attempting to identify the source of ROS that is required for LTP and memory, with a focus on a neuronally-expressed NADPH oxidase. In addition, we are working to identify redox-regulated proteins that may be targets of ROS during LTP and memory in the hippocampus.
Panel shows age-dependent effects on synpatic plasticity in extra-cellular SOD transgenic mice.
For recent examples of our work on this topic, please see:Kishida, K.T., Hoeffer, C.A., Hu, D., Pao, M., Holland, S.M., and Klann, E. (2006) Synaptic plasticity deficits and mild memory impairments in mouse models of chronic granulomatous disease. Mol. Cell. Biol. 26: 5908-5920.Kishida, K.T., Pao, M., Holland, S.M., and Klann, E. (2005) NADPH oxidase is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1. J. Neurochem. 94: 299-306.Tejada-Simon, M.V., Serrrano, F., Villasana, L.E., Kanterewicz, B.I., Wu, G.-Y., Quinn, M.T., and Klann, E. (2005) Synaptic localization of a functional NADPH oxidase in the mouse hippocampus. Mol. Cell. Neurosci. 29: 97-106.