AGE-RELATED-CHANGES IN LEARNING, MEMORY, AND LIPOFUSCIN AS A FUNCTIONOF THE PERCENTAGE OF SAMP8 GENES

SAMP8 (P8) mice are characterized by impaired learning and memory rela tively early in their life, while CD-1 mice show impairment later in l ife. 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 tr ained to avoid foot shock in a T-maze with retention tested 1 wk later . After testing, brain sections were examined for lipofuscin autofluor escence. At 4 mo of age, all strains, including the CD-1 and P8 strain s, showed no significant differences in learning, retention or lipofus cin deposits. At 12 mo of age, groups with 94%, 97% P8 genes or P8 mic e (100%) required significantly more trials to learn the task or relea rn the task 1 wk later than groups with 88% or fewer P8 genes. Lipofus cin deposits increased in the hippocampus as the percentage of P8 gene s increased suggesting that many genes control aging of the brain. How ever, the sudden appearance of impaired learning in the 94% strain sug gests 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.