Cited by 27Alzheimer's disease research and treatmentsNeurogenesis and neuroplasticity mechanismsDementia and Cognitive Impairment Research

The Retinoic Acid Receptor Agonist Am80 Increases Hippocampal ADAM10 in Aged SAMP8 Mice

Kitaoka, Kazuyoshi, Shimizu, Noriyuki, Ono, Koji, Chikahisa, Sachiko, Nakagomi, Madoka, Shudo, Koichi, Ishimura, Kazunori, Séi, Hiroyoshi +1 more·2013·Neuropharmacology

Abstract

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 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 (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 ADAM10-Notch-Hes5 proliferative pathway.

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Crossref · 10.1016/j.neuropharm.2013.04.009

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  • Vitamin A and retinoic acid administration improve Alzheimer's disease and age-related attenuation of memory/learning in mouse models, probably due to immunomodulatory effect and reduction of pro-inflammatory cytokines and chemokines production by astrocytes and microglia, as well as promotion of differentiation of neural stem cells and regeneration of neural cells.

    “Vitamin A and retinoic acid (a metabolite of all-trans-retinol) administration have been demonstrated to improve AD and age-related attenuation of memory/learning in mouse models, and this is probably due to their immunomodulatory effect and the reduction of pro-inflammatory cytokines and chemokines production by astrocytes and microglia, as well as to the promotion of differentiation of neural st”

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Authors
Kitaoka, K., Shimizu, N., Ono, K., Chikahisa, S., Nakagomi, M., Shudo, K., Ishimura, K., Séi, H., & Yoshizaki, K.
Affiliations
  • Tokushima University (JP)
  • Research Foundation ITSUU Laboratory (JP)
Corresponding author
Kitaoka, Kazuyoshi
Venue
Neuropharmacology
Publisher
Elsevier BV
Published
2013-09
Volume
72
Pages
58-65
ISSN
0028-3908 (ISSN-L)
OpenAlex
W2014227618
Cited by
27
References
42
Citations by year
2026: 1 · 2025: 3 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 2 · 2017: 7 · 2016: 4 · 2014: 1
FWCI
1.16
Type
journal article
Language
en
Open access
closed
Locations
  • Neuropharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science (23730706)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
retinoic acid receptor agonists, Am80, tamibarotene, ADAM10, retinoic acid, Alzheimer's disease, SAMP8 mice, aging, hippocampus, Notch signaling, Hes5, Ki-67, spatial working memory, amyloid precursor protein, amyloid-beta, neuroprotection
MeSH terms
ADAM10 Protein, Aging, Animals, Benzoates, Gene Expression Regulation, Hippocampus, Membrane Proteins, Memory, Short-Term, Mice, Mutant Strains, Repressor Proteins, RNA, Messenger, Tetrahydronaphthalenes, Time Factors, Receptors, Retinoic Acid, Maze Learning, Ki-67 Antigen, Cell Proliferation, Mice, ADAM Proteins, Basic Helix-Loop-Helix Proteins, Amyloid Precursor Protein Secretases

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