Oral administration of synthetic retinoid Am80 (Tamibarotene) decreases brain beta-amyloid peptides in APP23 mice.
The purpose of this study is to investigate whether a synthetic retinoid Am80 (tamibarotene) exhibits any improving effects on amyloid precursor protein (APP)23 mice, a model of Alzheimer's disease. Am80 was orally administered in feed to 20-week (5-month)-old APP23 mice at a dose of 0 (control) or 0.5 mg/kg/d for 14 weeks. The Am80 treatment reduced significantly the insoluble Abeta levels in brain, in particular Abeta(42), while it gave no apparent effects on the soluble Abeta levels. The results suggest that oral administration of Am80 may have potency to reduce the extracellular Abeta(42) of insoluble and possibly oligomeric or protofibril forms, which are related to the cause and/or progression of Alzheimer's disease. The Am80 treatment showed no significant effect on spatial learning and memory of APP23 mice by Morris water maze analysis. The main reason for the absence of significance seems based on the large deviation and some mice both in the treated and the non-treated groups would neither swim nor make efforts to reach the platform.
Kawahara
Kohichi
K
Department of Molecular Cell Function, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University.
Nishi
Kentaro
K
Suenobu
Michita
M
Ohtsuka
Hideyuki
H
Maeda
Akira
A
Nagatomo
Kenichiro
K
Kuniyasu
Akihiko
A
Staufenbiel
Matthias
M
Nakagomi
Madoka
M
Shudo
Koichi
K
Nakayama
Hitoshi
H
D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors* / Q000235:genetics; D000818:Animals; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000037:antagonists & inhibitors*; D012176:Retinoids / Q000008:administration & dosage / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology*
D016564:Amyloid beta-Protein Precursor; D001565:Benzoates; D010446:Peptide Fragments; D012176:Retinoids; D013764:Tetrahydronaphthalenes; C061133:tamibarotene