Age-related changes in learning, memory, and lipofuscin as a function of the percentage of SAMP8 genes

SAMP8 (P8) mice are characterized by impaired learning and memory relatively early in their life, while CD-1 mice show impairment later in life. A series of paternal backcross strains were developed from a CD-1 dame and P8 sire. Siblings from each backcross were bred to establish strains with 50% to 97% P8 genes. F4 mice, 4 or 12 mo of age, were trained to avoid foot shock in a T-maze with retention tested 1 wk later. After testing, brain sections were examined for lipofuscin autofluorescence. At 4 mo of age, all strains, including the CD-1 and P8 strains, showed no significant differences in learning, retention or lipofuscin deposits. At 12 mo of age, groups with 94%, 97% P8 genes or P8 mice (100%) required significantly more trials to learn the task or relearn the task 1 wk later than groups with 88% or fewer P8 genes. Lipofuscin deposits increased in the hippocampus as the percentage of P8 genes increased suggesting that many genes control aging of the brain. However, the sudden appearance of impaired learning in the 94% strain suggests that the mechanism(s) responsible for the impairment involves a few recessive genes and are independent of the mechanisms controlling the general aging of the brain.