The Retinoic Acid Receptor Agonist Am80 Increases Hippocampal ADAM10 in Aged SAMP8 Mice
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [109]
Cites
1 retracted
RETRACTED: SIRT1 Suppresses β-Amyloid Production by Activating the α-Secretase Gene ADAM10
Dönmez, G., Wang, D., Cohen, D. E., & Guarente, L. (2010) · Cell · doi:10.1016/j.cell.2010.06.020 · Cited by 433 · see citing works
RetractedA new murine model of accelerated senescence
Takeda, T., HOSOKAWA, M., TAKESHITA, S., Irino, M., Higuchi, K., Matsushita, T., Tomita, Y., Yasuhira, K., Hamamoto, H., & Shimizu, K. (1981) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(81)90084-1 · Cited by 871 · see citing works
Oscillatory Expression of the bHLH Factor Hes1 Regulated by a Negative Feedback Loop
Hirata, H., Yoshiura, S., Ohtsuka, T., Bessho, Y., Harada, T., Yoshikawa, K., & Kageyama, R. (2002) · Science · doi:10.1126/science.1074560 · Cited by 765 · see citing works
Oscillations in Notch Signaling Regulate Maintenance of Neural Progenitors
Shimojo, H., Ohtsuka, T., & Kageyama, R. (2008) · Neuron · doi:10.1016/j.neuron.2008.02.014 · Cited by 706 · see citing works
Hartmann, D. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.21.2615 · Cited by 680 · see citing works
Postina, R., Schroeder, A., Dewachter, I., Bohl, J., Schmitt, U., Kojro, E., Prinzen, C., Endres, K., Hiemke, C., Blessing, M., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20864 · Cited by 638 · see citing works
Notch signaling in the mammalian central nervous system: insights from mouse mutants
Yoon, K., & Gaiano, N. (2005) · Nature Neuroscience · doi:10.1038/nn1475 · Cited by 587 · see citing works
ADAMs family members as amyloid precursor protein α‐secretases
Allinson, T. M. J., Parkin, E. T., Turner, A. J., & Hooper, N. M. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10737 · Cited by 441 · see citing works
Assessment of spatial memory in mice
Sharma, S., Rakoczy, S. G., & Brown‐Borg, H. M. (2010) · Life Sciences · doi:10.1016/j.lfs.2010.09.004 · Cited by 370 · see citing works
Miyakawa, T., Yamada, M., Duttaroy, A., & Wess, J. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-14-05239.2001 · Cited by 366 · see citing works
The Notch-Hes pathway in mammalian neural development
Kageyama, R., & OHTSUKA, T. (1999) · Cell Research · doi:10.1038/sj.cr.7290016 · Cited by 343 · see citing works
Butterfield, D. A., & Poon, H. F. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.05.007 · Cited by 328 · see citing works
Senescence-accelerated mouse (SAM): a biogerontological resource in aging research
Takeda, T. (1999) · Neurobiology of Aging · doi:10.1016/s0197-4580(99)00008-1 · Cited by 311 · see citing works
Putative function of ADAM9, ADAM10, and ADAM17 as APP -secretase
Asai, M., Hattori, C., Szabó, B., Sasagawa, N., Maruyama, K., Tanuma, S.-I., & Ishiura, S. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)02999-6 · Cited by 303 · see citing works
Roles of Hes genes in neural development
Kageyama, R., Ohtsuka, T., & Kobayashi, T. (2008) · Development Growth & Differentiation · doi:10.1111/j.1440-169x.2008.00993.x · Cited by 284 · see citing works
Learning and memory in the SAMP8 mouse
Flood, J. F., & Morley, J. E. (1997) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(96)00063-2 · Cited by 267 · see citing works
Yagi, H., Katoh, S., Akiguchi, I., & Takeda, T. (1988) · Brain Research · doi:10.1016/0006-8993(88)90671-3 · Cited by 241 · see citing works
Kim, M., Suh, J., Romano, D., Truong, M. H., Mullin, K., Hooli, B., Norton, D., Tesco, G., Elliott, K., Wagner, S. L., et al. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp323 · Cited by 234 · see citing works
Takeda, T. (2009) · Neurochemical Research · doi:10.1007/s11064-009-9922-y · Cited by 233 · see citing works
Up‐regulation of the α‐secretase ADAM10 by retinoic acid receptors and acitretin
Tippmann, F., Hundt, J., Schneider, A., Endres, K., & Fahrenholz, F. (2009) · The FASEB Journal · doi:10.1096/fj.08-121392 · Cited by 224 · see citing works
β-Amyloid precursor polypeptide in SAMP8 mice affects learning and memory
Morley, J. E., Kumar, V. B., Bernardo, A. E., Farr, S. A., Uezu, K., Tumosa, N., & Flood, J. F. (2000) · Peptides · doi:10.1016/s0196-9781(00)00342-9 · Cited by 219 · see citing works
The senescence accelerated mouse (SAMP8) as a model for oxidative stress and Alzheimer's disease
Morley, J. E., Armbrecht, H. J., Farr, S. A., & Kumar, V. B. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.11.015 · Cited by 205 · see citing works
The SAMP8 Mouse: A Model to Develop Therapeutic Interventions for Alzheimers Disease
Morley, J. E., Farr, S. A., Kumar, V. B., & Armbrecht, H. J. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212799315795 · Cited by 169 · see citing works
Dynamic regulation of Notch signaling in neural progenitor cells
Kageyama, R., Ohtsuka, T., Shimojo, H., & Imayoshi, I. (2009) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.08.009 · Cited by 150 · see citing works
The ADAMs family: Coordinators of nervous system development, plasticity and repair
Yang, P., Baker, K. A., & Hagg, T. (2006) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2006.05.001 · Cited by 134 · see citing works
Age-related defects in lifespan and learning ability in SAMP8 mice
Nomura, Y., & Okuma, Y. (1999) · Neurobiology of Aging · doi:10.1016/s0197-4580(99)00006-8 · Cited by 93 · see citing works
Tamibarotene: A Candidate Retinoid Drug for Alzheimer’s Disease
Fukasawa, H., Nakagomi, M., Yamagata, N., Katsuki, H., Kawahara, K., Kitaoka, K., Miki, T., & Shudo, K. (2012) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b12-00314 · Cited by 91 · see citing works
Self-citationTowards Retinoid Therapy for Alzheimers Disease
Shudo, K., Fukasawa, H., Nakagomi, M., & Yamagata, N. (2009) · Current Alzheimer Research · doi:10.2174/156720509788486581 · Cited by 91 · see citing works
Self-citationMiwako, I., & Kagechika, H. (2007) · Drugs of today · doi:10.1358/dot.2007.43.8.1072615 · Cited by 84 · see citing works
Neurochemistry, Neuropathology, and Heredity in SAMP8: A Mouse Model of Senescence
Tomobe, K., & Nomura, Y. (2009) · Neurochemical Research · doi:10.1007/s11064-009-9923-x · Cited by 83 · see citing works
Jarvis, C. I., Goncalves, M. B. C. V., Clarke, E. E., Dogruel, M., Kalindjian, S. B., Thomas, S. A., Maden, M., & Corcoran, J. P. T. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07426.x · Cited by 78 · see citing works
Soleus muscles of SAMP8 mice provide an accelerated model of skeletal muscle senescence
Derave, W., Eijnde, B. O., Ramaekers, M., & Hespel, P. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.05.005 · Cited by 69 · see citing works
Bernstein, H., Bukowska, A., Krell, D., Bogerts, B., Ansorge, S., & Lendeckel, U. (2003) · Journal of Neurocytology · doi:10.1023/b:neur.0000005600.61844.a6 · Cited by 68 · see citing works
Vitamin A deficiency induces motor impairments and striatal cholinergic dysfunction in rats
Carta, M., Stancampiano, R., Tronci, E., et al. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.01.027 · Cited by 54 · see citing works
Limited hippocampal neurogenesis in SAMP8 mouse model of Alzheimer's disease
Gang, B., Yue, C., Han, N., Xue, H., Li, B., Sun, L., Li, X., & Zhao, Q. (2011) · Brain Research · doi:10.1016/j.brainres.2011.03.039 · Cited by 36 · see citing works
Tubular aggregates in the skeletal muscle of the senescence-accelerated mouse; SAM
Nishikawa, T., Takahashi, J. A., Matsushita, T., Ohnishi, K., Higuchi, K., Hashimoto, N., & Hosokawa, M. (2000) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(00)00088-9 · Cited by 32 · see citing works
Selective vulnerability of neocortical association areas in Alzheimer's disease
Giannakopoulos, P., Hof, P. R., & Bouras, C. (1998) · Microscopy Research and Technique · doi:10.1002/(sici)1097-0029(19981001)43:1 · Cited by 31 · see citing works
Evidence against a role for rare ADAM10 mutations in sporadic Alzheimer Disease
Cai, G., Atzmon, G., Naj, A. C., Beecham, G. W., Barzilai, N., Haines, J. L., Sano, M., Pericak‐Vance, M. A., & Buxbaum, J. D. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.03.003 · Cited by 30 · see citing works
Mori, D., Katayama, T., Miyake, H., et al. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.12.004 · Cited by 28 · see citing works
Song, J., Yu, J., Liu, M., Yan, C., & Tan, L. (2011) · Brain Research · doi:10.1016/j.brainres.2011.09.008 · Cited by 25 · see citing works
Fischer, H. S., Berti, I., Schatz, D. S., et al. (2000) · Regulatory Peptides · doi:10.1016/s0167-0115(00)00201-9 · Cited by 11 · see citing works
Kitaoka, K., Sano, A., Chikahisa, S., Yoshizaki, K., & Séi, H. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.01.059 · Cited by 9 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence
Varesi, A., Chirumbolo, S., Campagnoli, L. I. M., Pierella, E., Piccini, G. B., Carrara, A., Ricevuti, G., Scassellati, C., Bonvicini, C., & Pascale, A. (2022) · Antioxidants · doi:10.3390/antiox11071224 · Cited by 145 · see citing works
Mechanistic Insights for Drug Repurposing and the Design of Hybrid Drugs for Alzheimer’s Disease
Padhi, D., & Govindaraju, T. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00335 · Cited by 47 · see citing works
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review