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 &beta; (A&beta;) 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 A&beta;-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 A&beta;-positive granules in the hippocampus. These results suggest that ZSET1446 shows ameliorating effects on SAMP8 partly due to the suppression of an increase of A&beta;-deposition in the hippocampus.
Central Research Laboratory, Zenyaku Kogyo Co, Ltd, Tokyo, Japan. Yoshimasa_Yamaguchi@mail.zenyaku.co.jp
Yoshimasa
Y
Yamaguchi
Kenichi
K
Saito
Toshiyuki
T
Matsuno
Kentaro
K
Takeda
Masataka
M
Hino
D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D013141:Spiro Compounds / Q000494:pharmacology / Q000627:therapeutic use*
D016229:Amyloid beta-Peptides; D007189:Indans; D018696:Neuroprotective Agents; D013141:Spiro Compounds; C511224:spiro(imidazo-(1,2-a)pyridine-3,2-indan)-2(3H)-one