Altered gene expression in the brain of senescence accelerated mouse SAMP8

Abstract

In an attempt to find molecular biological differences between SAMP8 and SAMR1, we investigated age-related changes in the expression of selected genes (cyclophilin, actin, hsc70 and hsp90) in different brain regions (cerebrum, brain stem and cerebellum). The patterns of expression of these genes were remarkably different from each other in all brain regions of both strains from the time of weaning throughout their life. However, when the level of gene expression in the same sex of the two strains was expressed as a percentile of respective average life span, the timing and intensity of gene expression was found to be nearly identical despite the twofold difference in their life spans. It was of interest to examine when such accelerated gene expression begins in the brain of SAMP8. We further investigated the postnatal expression of cyclophilin and hsc70 mRNAs. There was no significant difference between the two strains in the expression pattern of the mRNAs from postnatal (day 4) to weaning (about day 20) in all brain regions examined, suggesting that the acceleration of gene expression may begin at or soon after weaning. On the other hand, myelin basic protein (MBP) mRNA, which is expressed postnatally in mouse, was first detected after birth at day 4 in all brain regions examined, increased dramatically to a peak at about day 16 and gradually decreased thereafter with advancing age (day 30 to 50). In the cerebrum and brain stem, no appreciable difference in the expression pattern of MBP mRNA was observed between these strains. In the cerebellum, however, the age-increased MBP mRNA level in SAMP8 began to decline at day 20 when the mRNA level remained relatively high in SAMR1. The decline of MBP mRNA level in the cerebellum of SAMP8 after weaning might cause impaired myelin formation that leads to the learning-memory deficit that is observed early in life. Such altered gene expression in the brain and possibly other tissues may also be relevant to accelerated aging of this strain of mouse.