Biochemical changes in the brain of the senescence-accelerated mouse P8 and P10

Abstract

We found a significant elevation in the IL-1β mRNA content in the hippocampus of SAMP8 in comparison with that of SAMR1 at 10 months after birth. In both senescence-accelerated mouse (SAM) strains, the increases in brain IL-1β protein were more noticeable at 10 months than at 2 or 5 months. The only differences found in protein levels between strains were at 10 months and consisted of elevations in TNFα and IL-6 in the cerebral cortex and the hippocampus as well as in IL-1β in the hippocampus and the hypothalamus, as compared with SAMR1. The increases in expression of these proinflammatory cytokines in the brain seem to be involved in the age-related neuronal dysfunction and/or learning deficiency in SAMP8. With regard to SAMP10, we performed behavioral and neurochemical studies and found evidence of depression in both tail suspension and forced swimming tests as well as an increase in D 2 dopamine receptors and 5-HT 1A receptors in the cortex and the midbrain at 7 months in SAMP10, suggesting that the SAMP10 strain provides a useful model of age-associated depression. We also report that a reduction of muscarinic acetylcholine receptors and protein kinase C in the brain could underlie learning dysfunction in SAMP10.