Age-related changes in nitric oxide content and nitric oxide synthase activity in senescence-accelerated mouse (SAMP8) brain

Abstract

The senescence-accelerated mouse (SAM), where average lifespan is about 70% compared with other strains, was established as a murine model of accelerated aging (Takeda et al., 1981). SAM was selected from the sister-brother mating of AKR strain mice. The pattern of aging in SAM is that of accelerated senescence which begins after normal development, i.e., not related to premature aging or senescence. The SAM strains have been designated as SAMP1, SAMP2, SAMP3, SAMP4, SAMP6, and SAMP8 based on the signs of aging and gross lesions (Miyamoto et al., 1986). Because the SAMP8 strain exhibited inferior acquisition of learning from 4 months onwards with a low incidence of senile amyloidosis (Miyamoto et al., 1986), it was thought to be an excellent animal model of deficits in learning and memory. Though SAMP8 mice showed age-related memory and learning deficit which was linked to a deterioration in the ability of acquisition in multiple-trial passive avoidance response, their T-maze performances, which reflect working and reference memory, were essentially normal (Yagi et al., 1988). Because deficits in working and reference memories are thought to be closely related to septal and/or hippocampal damage (Stanton et al., 1984), SAMP8 are thought to have little or no damage in these areas (Yagi et al., 1988).