Age-related expression of adenosine receptors in brain from the senescence-accelerated mouse

Abstract

Senescence-accelerated mice (SAM) are used as a model of aging and age-associated diseases. SAMP8 are prone strains that show shortened life span and deficits in learning and memory processes, while SAMR1 are strains of accelerated senescence-resistant, long-lived mice. Due to their abnormal APP (amyloid precursor protein) metabolism in brain, SAMP8 may be an Alzheimer-type model. Adenosine receptors are G-protein coupled receptors which are altered in brain from Alzheimer disease (AD) cases. The analysis of adenosine receptors in brain from young (21 days old) and middle-aged (180 days old) SAMP8 as compared with SAMR1 mice revealed differences between these strains associated with age. The age-related increase in mRNA coding A 1 and A 2B receptors observed in SAMR1 was absent in SAMP8. A 1 receptors were significantly decreased with age in SAMR1, while no differences were observed in SAMP8. However, the levels of A 1 receptors in young SAMP8 were even lower than those obtained in middle-aged SAMR1. In addition, A 2A receptors were significantly increased only in aged SAMR1. A similar age-related decrease in A 1 receptors level was also observed in brain from male Wistar rats. These results suggest different age-related effects on adenosine receptors in SAMR1 and SAMP8 strains. Since A 1 receptors are mainly neuroprotective, their important loss in very young SAMP8 strain suggests the involvement of these receptors in the pathogenesis of neurodegenerative diseases associated with aging.