Yasunobu Okuma and Yasuyuki Nomura
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Abstract: To elucidate the fundamental mechanism of age-related deficiencies of learning and to develop effective drugs for intervention in age-related diseases such as learning dysfunctions, pertinent animal models that have characteristics closely similar to human dysfunctions should be established. SAM (senescence-accelerated mouse) has been established as a murine model of the SAM strains, groups of related inbred strains including nine strains of accelerated senescence-prone, short-lived mice (SAMP) and three strains of accelerated senescence-resistant, long-lived mice (SAMR). SAMP-strain mice show relatively strain-specific age-associated phenotypic pathologies such as shortened life span and early manifestation of senescence. Among the SAMP-strain mice, SAMP8 mice show an age-related deterioration in learning ability. Here, the neuropathological, neurochemical and pharmacological features of SAM are reported, especially for SAMP8. Moreover, the effects of several drugs on the biochemical and behavioral alterations in SAMP8 and the etiologic manifestation of accelerated senescence are also discussed.
Keywords: Senescence-accelerated mouse (SAM), Senile dementia, Animal model, Learning and memory, Aging