AGED AMYLOID PRECURSOR PROTEIN TRANSGENIC MICE
ARE IMPAIRED IN NEURONAL PLASTICITY
A.R. Koudinov1,2 , 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 wild type human amyloid precursor protein (APP695) at age 4-5 and 16.5 months have cognitive behavioral deficit while maintaining unaffected long term potentiation (LTP) in the CA1 area of the hippocampus (Koudinov et al, Soc Neurosci Abstr 25(2):1860 [1999]). The aim of the present study was to test whether aged APP mice express neuronal plasticity deficit. To this end synaptic physiology and tetanus induced (t) LTP was studied in 25.5 month old APP and corresponding control wild type (WT) mouse hippocampal slices using extracellular 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. WT and APP TG were not significantly different in I/O characteristics of the slices, although WT slices tended to have higher responses for similar stimulus intensity. On the other hand, TG and WT slices were different in both induction and maintanance of the LTP. The amount of initial post-tetanic potentiation of APP TG and WT control slices reached statistical significance (37.3 ± 9.2%, n=7 and 95.1 ± 26.2%, n = 10, respectively, p = 0.0075). Within 5 min potentiation, APP TG levels dropped to near baseline values, whereas control WT slices remained potentiated (2.1 ± 1.2%, n=7 and 50.6 + 16.2%, n=10, respectively, p=0.012) and maintained LTP throughout the 15 min post-tetanic recording time. There were no significant differences in induction (P=0.2403) and maintanance (probed at 5 min after tetanus, P=0.0649) of the LTP in WT slices taken from 25.5 and 16.5 months old mice. On the other hand APP TG slices expressed significant decline in both induction (P=0.0047) and maintanance (P=0.0048) of the LTP between the indicated ages. Our data suggest that human APP overexpression causes a decline in neuronal plasticity in aged mice.
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