Although we have found that reactive oxygen species (ROS) are required for full expression of hippocampal LTP and memory, it is clear that the aged and diseased brain handle ROS much differently as many studies have pointed to a role for excessive ROS and oxidative stress in age-related cognitive decline and impaired memory associated with Alzheimer's disease. Over the past five years, we have studied the role of ROS in aging-related impairments in LTP and memory that are associated with normal aging, and have conducted studies to identify sources of ROS responsible for oxidative stress in mice that model Alzheimer's disease. In addition, we are attempting to identify downstream effectors of oxidative stress, particularly of mitochondrial-derived ROS, in mice that model Azlheimer's disease.
Image panel showing enhanced levels of superoxide in area CA1 of the hippocampal sections treated with amyloid β peptide, to mimic Alzheimer's disease condition as compared to untreated controls. This enhanced oxidative stress can be rescued using Glucagon-like Peptide 1 cleavage product.
For recent selected examples of our work on this topic, please see:Ma, T. and Klann, E. (2012) Amyloid b: linking synaptic plasticity failure to memory disruption in Alzheimer's disease. J. Neurochem. 120: 140-148.Ma, T., Hoeffer, C.A., Wong, H., Massaad, C.A., Zhou, P., Iadecola, C., Murphy, M.P., Pautler, R.G., and Klann, E. (2011) Amyloid b-induced impairments in hippocampal synaptic plasticity are rescued by decreasing mitochondrial superoxide. J. Neurosci. 31: 5589-5595.Ma, T., Hoeffer, C.A., Capetillo-Zarate, E., Yu, F., Wong, H., Tampellini, D., Klann, E., Blitzer, R.D., and Gouras, G.K. (2010) Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease. PLoS One 5: e12845.Massaad, C.A., Amin, S.K., Hu, L., Mei, Y., Klann, E., and Pautler, R.G. (2010) Mitochondrial superoxide contributes to blood flow and axonal transport deficits in the Tg2576 mouse model of Alzheimer's disease. PLoS One 5: e00561.Massaad, C.A., Washington, T.M., Pautler, R.G., and Klann, E. (2009) Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer's disease. Proc. Natl. Acad. Sci. USA 106: 13576-13581.Massaad, C.A., Pautler, R.G., and Klann, E. (2009) Mitochondrial superoxide: a key player in Alzheimer's disease. Aging 1: 758-761.Hu, D., Cao, P., Thiels, E., Chu, C.T., Wu, G.-Y., Oury, T., and Klann, E. (2007) Hippocampal long-term potentiation, memory, and longevity in mice that overexpress mitochondrial superoxide dismutase. Neurobiol. Learn. Mem. 87: 372-384.