The retinoic acid receptor agonist Am80 increases hippocampal ADAM 10 in aged SAMP8 mice

作者：Kitaoka Kazuyoshi^*; Shimizu Noriyuki; Ono Koji; Chikahisa Sachiko; Nakagomi Madoka; Shudo Koichi; Ishimura Kazunori; Sei Hiroyoshi; Yoshizaki Kazuo

来源：Neuropharmacology, 2013, 72: 58-65.

DOI：10.1016/j.neuropharm.2013.04.009

• Aging
• Dementia
• Vitamin A
• Hes5
• Ki67

The retinoic acid (RA, a vitamin A metabolite) receptor (RAR) is a transcription factor. Vitamin A/RA administration improves the Alzheimer%26apos;s disease (AD)- and age-related attenuation of memory/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 (A beta), and hairy/enhancer of split (Hes), which are mediated by ADAM10. Spatial working memory and the levels of a hippocampal proliferation marker (1067) 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 1067 were restored and the deterioration of working memory was suppressed, whereas APP and A beta levels remained unchanged. Our results suggest that Am80 administration effectively improves dementia by activating the hippocampal ADAM10-Notch-Hes5 proliferative pathway.

• 出版日期2013-9