Effects of ZSET1446/ST101 on cognitive deficits and amyloid β deposition in the senescence accelerated prone mouse brain.
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| Abstract |
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.
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| Authors | Yoshimasa Yamaguchi, Kenichi Saito, Toshiyuki Matsuno, Kentaro Takeda, Masataka Hino |
| Journal | Journal of pharmacological sciences (J Pharmacol Sci) Vol. 119 Issue 2 Pg. 160-6 ( 2012) ISSN: 1347-8648 [Electronic] Japan |
| PMID | 22790316 (Publication Type: Journal Article) |
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