The retinoic acid receptor agonist Am80 increases hippocampal ADAM10 in aged SAMP8 mice

Kazuyoshi Kitaoka
Noriyuki Shimizu
Koji Ono
Sachiko Chikahisa
Madoka Nakagomi
Koichi Shudo
Kazunori Ishimura
Hiroyoshi Séi
Kazuo Yoshizaki

The retinoic acid (RA, a vitamin A metabolite) receptor (RAR) is a transcription factor. Vitamin A/RA administration improves the Alzheimer's disease (AD)- and age-related attenuation ofmemory/learning in mouse models. Recently, a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10)was identified as a key molecule in RA-mediated anti-AD mechanisms. We investigated the effect of chronic administration of the RAR agonist Am80 (tamibarotene) on ADAM10 expression in senescence-accelerated mice (SAMP8).Moreover, we estimated changes in the expression of the amyloid precursor protein (APP), amyloid beta (Aβ), and hairy/enhancer of split (Hes), which are mediated by ADAM10. Spatial working memory and the levels of a hippocampal proliferation marker (Ki67) were also assessed in these mice. ADAM10 mRNA and protein expression was significantly reduced in the hippocampus of 13-month-old SAMP8 mice
 their expression improved significantly after Am80 administration. Further, after Am80 administration, the expression levels of Hes5 and Ki67 were restored and the deterioration of working memory was suppressed, whereas APP and Aβ levels remained unchanged. Our results suggest that Am80 administration effectively improves dementia by activating the hippocampal ADAM10eNotcheHes5 proliferative pathway. © 2013 Elsevier Ltd. All rights reserved.

Neuropharmacology

Elsevier Ltd

72

58

65

10.1016/j.neuropharm.2013.04.009

https://doi.org/10.1016/j.neuropharm.2013.04.009
https://www.ncbi.nlm.nih.gov/pubmed/23624141