Senescence-accelerated mouse prone 6 (SAMP6) mice exhibit increased expression of NMDA receptor NR2B subunit (NR2B) and improved short-term memory compared with senescence-accelerated mouse resistance 1 (SAMR1) mice. The Thr286 phosphorylation of alpha calcium/calmodulin-dependent protein kinase II (CaMKII) has a crucial role in plasticity and learning among multiple downstream signaling pathways linked to the NMDA receptor. To examine the relationship between CaMKII activity and spatial learning in SAMP6, the authors employed western blot analysis and behavioral analyses (object location and delayed spatial win-shift eight-arm radial-maze tests). The levels of Thr286 and Ser831 phosphorylation of CaMKII and AMPA receptor subunit glutamate receptor 1 (CaMKII substrate), respectively, were increased in hippocampus of SAMP6 compared with SAMR1. SAMP6 showed faster hippocampal-dependent spatial memory formation than SAMR1 in both the object location and win-shift eight-arm radial-maze tests. Our results indicate that increased CaMKII activity influences the NR2B/CaMKII signal pathway and cognitive function in SAMP6.
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