ABSTRACT
INTRODUCTION: Age associated cognitive impairment is associated with low levels of IGF-1, oxidative stress, and neuronal loss in the hippocampus. Ames dwarf mice are long-lived animals that exhibit peripheral IGF-1 deficiency. Hippocampal-based spatial memory (a homolog of cognitive function) has not been evaluated in these long-living mice. MATERIALS AND METHODS: We evaluated the hippocampal-based spatial memory in 3-, 12- and 24-month-old Ames dwarf and wild type mice using the Barnes maze and the T-maze. We also examined the effect of a hippocampal-specific toxin, kainic acid (KA), on spatial memory to determine whether Ames mice were resistant to the cognitive impairment induced by this compound. RESULTS: We found that Ames dwarf mice exhibit enhanced learning, making fewer errors and using less time to solve both the Barnes and T-mazes. Dwarf mice also have significantly better short-term memory as compared to wild type mice. Both genotypes exhibited neuronal loss in the CA1 and CA3 areas of the hippocampus following KA, but Ames dwarf mice retained their spatial memory. DISCUSSION: Our results show that Ames dwarf mice retained their spatial memory despite neurodegeneration when compared to wild type mice at an "equiseizure" dose of KA.
