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Upregulated expression of a subset of genes in APP;ob/ob mice: Evidence of an interaction between diabetes‐linked obesity and Alzheimer’s disease

Clinical studies have indicated that obesity and diabetes are associated with Alzheimer's disease (AD) and neurodegeneration. However, the mechanism by which obesity/diabetes and AD interact with each other and contribute to dementia remains elusive. To obtain insights into their interaction at...

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Autores principales: Shinohara, Mitsuru, Kikuchi, Masataka, Onishi‐Takeya, Miyuki, Tashiro, Yoshitaka, Suzuki, Kaoru, Noda, Yasuhiro, Takeda, Shuko, Mukouzono, Masahiro, Nagano, Seiichi, Fukumori, Akio, Morishita, Ryuichi, Nakaya, Akihiro, Sato, Naoyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103720/
https://www.ncbi.nlm.nih.gov/pubmed/33977233
http://dx.doi.org/10.1096/fba.2020-00151
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author Shinohara, Mitsuru
Kikuchi, Masataka
Onishi‐Takeya, Miyuki
Tashiro, Yoshitaka
Suzuki, Kaoru
Noda, Yasuhiro
Takeda, Shuko
Mukouzono, Masahiro
Nagano, Seiichi
Fukumori, Akio
Morishita, Ryuichi
Nakaya, Akihiro
Sato, Naoyuki
author_facet Shinohara, Mitsuru
Kikuchi, Masataka
Onishi‐Takeya, Miyuki
Tashiro, Yoshitaka
Suzuki, Kaoru
Noda, Yasuhiro
Takeda, Shuko
Mukouzono, Masahiro
Nagano, Seiichi
Fukumori, Akio
Morishita, Ryuichi
Nakaya, Akihiro
Sato, Naoyuki
author_sort Shinohara, Mitsuru
collection PubMed
description Clinical studies have indicated that obesity and diabetes are associated with Alzheimer's disease (AD) and neurodegeneration. However, the mechanism by which obesity/diabetes and AD interact with each other and contribute to dementia remains elusive. To obtain insights into their interaction at molecular levels, we performed gene expression analysis of APP;ob/ob mice, which were generated by crossing transgenic AD model mice (APP23 mice) with ob/ob mice, which are obese and mildly diabetic. The Aβ level in these mice was reduced compared with that in pure APP mice. However, we identified a cluster of genes (cluster 10) upregulated in APP;ob/ob mice but not in either APP or ob/ob mice. Interestingly, genes upregulated in the human AD brain were enriched in cluster 10. Moreover, genes in cluster 10 formed a network and shared upregulated genes with a cell model of neurodegeneration and other models of neurological disorders such as ischemia and epilepsy. In silico analyses showed that serum response factor (SRF), recently identified in a single‐cell analysis of human brains as a transcription factor that can control the conversion from healthy cells to AD cells, might be a common transcriptional regulator for a subset of cluster 10 genes. These data suggest that upregulation of genes uniquely associated with APP;ob/ob mice is an evidence of the interaction between obesity/diabetes and AD.
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spelling pubmed-81037202021-05-10 Upregulated expression of a subset of genes in APP;ob/ob mice: Evidence of an interaction between diabetes‐linked obesity and Alzheimer’s disease Shinohara, Mitsuru Kikuchi, Masataka Onishi‐Takeya, Miyuki Tashiro, Yoshitaka Suzuki, Kaoru Noda, Yasuhiro Takeda, Shuko Mukouzono, Masahiro Nagano, Seiichi Fukumori, Akio Morishita, Ryuichi Nakaya, Akihiro Sato, Naoyuki FASEB Bioadv Research Articles Clinical studies have indicated that obesity and diabetes are associated with Alzheimer's disease (AD) and neurodegeneration. However, the mechanism by which obesity/diabetes and AD interact with each other and contribute to dementia remains elusive. To obtain insights into their interaction at molecular levels, we performed gene expression analysis of APP;ob/ob mice, which were generated by crossing transgenic AD model mice (APP23 mice) with ob/ob mice, which are obese and mildly diabetic. The Aβ level in these mice was reduced compared with that in pure APP mice. However, we identified a cluster of genes (cluster 10) upregulated in APP;ob/ob mice but not in either APP or ob/ob mice. Interestingly, genes upregulated in the human AD brain were enriched in cluster 10. Moreover, genes in cluster 10 formed a network and shared upregulated genes with a cell model of neurodegeneration and other models of neurological disorders such as ischemia and epilepsy. In silico analyses showed that serum response factor (SRF), recently identified in a single‐cell analysis of human brains as a transcription factor that can control the conversion from healthy cells to AD cells, might be a common transcriptional regulator for a subset of cluster 10 genes. These data suggest that upregulation of genes uniquely associated with APP;ob/ob mice is an evidence of the interaction between obesity/diabetes and AD. John Wiley and Sons Inc. 2021-03-02 /pmc/articles/PMC8103720/ /pubmed/33977233 http://dx.doi.org/10.1096/fba.2020-00151 Text en © 2021 The Authors. FASEB BioAdvances published by the Federation of American Societies for Experimental Biology https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research Articles
Shinohara, Mitsuru
Kikuchi, Masataka
Onishi‐Takeya, Miyuki
Tashiro, Yoshitaka
Suzuki, Kaoru
Noda, Yasuhiro
Takeda, Shuko
Mukouzono, Masahiro
Nagano, Seiichi
Fukumori, Akio
Morishita, Ryuichi
Nakaya, Akihiro
Sato, Naoyuki
Upregulated expression of a subset of genes in APP;ob/ob mice: Evidence of an interaction between diabetes‐linked obesity and Alzheimer’s disease
title Upregulated expression of a subset of genes in APP;ob/ob mice: Evidence of an interaction between diabetes‐linked obesity and Alzheimer’s disease
title_full Upregulated expression of a subset of genes in APP;ob/ob mice: Evidence of an interaction between diabetes‐linked obesity and Alzheimer’s disease
title_fullStr Upregulated expression of a subset of genes in APP;ob/ob mice: Evidence of an interaction between diabetes‐linked obesity and Alzheimer’s disease
title_full_unstemmed Upregulated expression of a subset of genes in APP;ob/ob mice: Evidence of an interaction between diabetes‐linked obesity and Alzheimer’s disease
title_short Upregulated expression of a subset of genes in APP;ob/ob mice: Evidence of an interaction between diabetes‐linked obesity and Alzheimer’s disease
title_sort upregulated expression of a subset of genes in app;ob/ob mice: evidence of an interaction between diabetes‐linked obesity and alzheimer’s disease
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103720/
https://www.ncbi.nlm.nih.gov/pubmed/33977233
http://dx.doi.org/10.1096/fba.2020-00151
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