AGE-RELATED-CHANGES IN LEVELS OF THE BETA-SUBUNIT OF NERVE GROWTH-FACTOR IN SELECTED REGIONS OF THE BRAIN - COMPARISON BETWEEN SENESCENCE-ACCELERATED (SAM-P8) AND SENESCENCE-RESISTANT (SAM-R1) MICE

Senescence-accelerated mice (SAM-P8) are characterized as mice in which aging is accelerated and memory disturbances occur. In several regions in the brain of SAM-P8 mice at 2, 4 and 8 months of age, we examined the concentrations of the beta-subunit of nerve growth factor (beta-NGF) and nine kinds of proteins such as S100 beta and alpha B-crystallin, and compared them with those in senescence-resistant mice (SAM-R1, as controls) at corresponding ages. Levels of beta-NGF in the hippocampus of SAM-R1 and SAM-P8 mice were reduced at 8 months of age. However, the decrease was more conspicuous in SAM-R1 than in SAM-P8, resulting in a significant difference between them (P < 0.01). The concentrations of beta-NGF in the cerebral cortex and cerebellum decreased to some extent with age in the control mice while it remained unchanged in the mutant mice. By contrast, the olfactory bulbs from SAM-R1 and SAM-P8 retained almost constant levels of beta-NGF during the first 8 months. However, its level was already higher in SAM-P8 at 2 months than in SAM-R1. Among nine proteins measured here, the acceleration of age-related increase was apparent in the levels of S100 beta and Mn-SOD in the cerebral cortex from SAM-P8. By contrast, the cerebral cortex and cerebellum from SAM-P8 showed tendencies to contain significantly high levels of alpha B-crystallin. These results suggest, at]east, the presence of fibrous gliosis at quite an early age as well as the acceleration of senescence, in selected regions of the brain of SAM-P8.