DISSOCIATED INVOLVEMENT OF Cu/Zn-SUPEROXIDE DISMUTASE AND AMYLOID PRECURSOR PROTEIN IN NEURONAL AND BEHAVIORAL PLASTICITY
A.R. Koudinov1,2* , C. Cerruti1, Y. Groner1 and M. Segal1
1. Weizmann Institute of Science, Department of Neurobiology and Molecular Genetics, Rehovot 76100, Israel
2. Russian Academy of Medical Sciences, National Mental Health Research Center, Institute of Biomedical Chemistry, Timoshenko 38-27, Moscow 121359, Russian Federation
We have previously reported that transgenic mice (TG) expressing human Cu/Zn-Superoxide Dismutase (SOD), and thus modeling chronic oxidative stress, have cognitive behavioral deficits and do not maintain long term potentiation (LTP) in the CA1 area of the hippocampus (Eur J Neurosci 1998, 10: 538; Neurosci Lett 1998, 51: S23). The aim of the present study was to elucidate the combined effect of SOD and human amyloid precursor protein (APP) expression on TG neuronal plasticity. To this end synaptic physiology and tetanus induced (t) LTP was studied in TG and corresponding control mouse hippocampal slices usingextracellular recording of CA1 field excitatory postsynaptic potentials (fEPSPs). The input/output relationship and tLTP were expressed as a fEPSP slope change versus stimulus intensity and time, respectively. At ages 4-5 and 16-17 months, only mice overexpressing SOD or both SOD and APP have impaired tLTP. The mice, overexpressing APP alone showed no tLTP impairment. At age 16-17 months the amount of initial post-tetanic potentiation in both APP and SOD-APP mice did not differ significantly from the corresponding controls. APP TG slices maintained tLTP throughout the 20 min post-tetanic recording time (50.7±8.7%), while SOD-APP TG slices dropped to near baseline values (5.8±1.6%). Behaviorally, SOD-APP mice were much more impaired in spatial memory tasks then the single transgenes. This impairment was more severe in the older age group. Thus, a dissociation between behavioral and neuronal plasticity in SOD-APP transgenic mice is evident.
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