Age-related changes in learning and memory in the senescence-accelerated mouse (SAM)

Abstract

Age-related changes in learning ability were studied in senescence-accelerated mice (SAM) reared under specific pathogen-free (SPF) conditions. SAM-P/8/Ta (SAM-P/8, senescence-prone substrain) showed an age-associated increase in spontaneous motor activity (SMA) compared with SAM-R/1/Ta (SAM-R/1, senescence-resistant substrain) in a novel environment when the activity was measured in the light period, although there was no significant difference in the dark period. In observations of the circadian rhythm of SMA, SAM-P/8 showed a significant increase in diurnal SMA. In SAM-P/8 mice, the acquisition of passive avoidance response was slightly but significantly impaired even at 2 months of age, compared with SAM-R/1 control; the impairment became obvious with aging. In a one-way active avoidance task, SAM-P/8 did not show any impairment in the acquisition of avoidance response at 2 and 4 months of age. However, significant impairment was observed in SAM-P/8 at 12 months of age. The impairments of avoidance tasks were not due to a decrease in shock sensitivity, as indicated by no significant change in the flinch-jump threshold. In a water-filled multiple T-maze task, there was no difference in the number of errors between the two groups. With regard to the performance time to reach the goal, however, SAM-P/8 showed a mild prolongation at 2 months of age, and the prolongation became marked with advancing age. Furthermore, SAM-P/8 showed an age-related increase in the latency to escape onto the hidden platform in the Morris water task as compared with the control mice, whereas a slight but significant impairment was observed even at 2 months of age. These results indicate that SAM-P/8 shows age-related deterioration of ability in learning and memory, and the two factors of genetic strain difference and acceleration of aging are likely to be involved in the deterioration observed in SAM-P/8. Also, it is suggested that SAM-P/8 may be useful as an experimental animal model for senile memory impairment in humans.