Effects of ZSET1446/ST101 on cognitive deficits and amyloid β deposition in the senescence accelerated prone mouse brain

The senescence accelerated prone mouse strain 8 (samp8) develops age-related deficits in learning and memory. effects of the azaindolizinone derivative zset1446/st101,a newly synthesized cognitive enhancer,on cognitive impairment and deposition of amyloid β (aβ) were assessed in the samp8. zset1446 was administered in drinking water at estimated doses of 0.002,0.01,and 0.1 mg/kg per day from the age of 8 months. the samp8 at the age of 8 months showed cognitive impairment in a novel object recognition task compared with young samp8 at the age of 8 weeks. further,grading scores were gradually increased from 9 to 12 months and aβ-like immunoreactivity in the hippocampus was increased at the age of 10 months. zset1446 ameliorated cognitive deficits of samp8 after 4,8,12,and 16 weeks of treatment in a novel object recognition test. zset1446 also reduced grading scores of samp8 after 16 weeks of treatment. further,8-week treatment of zset1446 significantly reduced the total number of aβ-positive granules in the hippocampus. these results suggest that zset1446 shows ameliorating effects on samp8 partly due to the suppression of an increase of aβ-deposition in the hippocampus. © the japanese pharmacological society.