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Disruption of Circadian Clocks Promotes Progression of Alzheimer’s Disease in Diabetic Mice

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Abstract

The circadian clock is an endogenous system designed to anticipate and adapt to daily changes in the environment. Alzheimer’s disease (AD) is a progressive neurodegenerative disease, which is more prevalent in patients with type 2 diabetes mellitus (T2DM). However, the effects of circadian disruption on mental and physical health for T2DM patients are not yet fully understood, even though circadian disruption has been confirmed to promote the progression of AD in population. By housing db/db mice on a disrupted (a 6:18 light/dark cycle) circadian rhythm, we assessed the circadian gene expression, body weight, cognitive ability, and AD-related pathophysiology. Our results indicated that housing in these conditions led to disrupted diurnal circadian rhythms in the hippocampus of db/db mice and contributed to their weight gain. In the brain, the circadian-disrupted db/db mice showed a decreased cognitive ability and an increased hyperphosphorylation of tau protein, even though no difference was found in amyloid protein (Aβ) plaque deposition. We also found that the hyperphosphorylated tau protein exhibited more disruptive daily oscillations in db/db mice hippocampus under the 6:18 light/dark cycle. Circadian alterations could promote the development of AD in T2DM.

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Acknowledgements

We thank Danpei Li and Li Huang from Huazhong University of Science and Technology for the technical advice and assistance with this study.

Funding

This work was supported by the National Natural Science Foundation of China (Grants 81670754, 81800686, and 81974114) and funds of Jie Chu Jing Ying Foundation (Grants 2018076).

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Authors and Affiliations

  1. Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China

    Jiaojiao Huang, Xuemin Peng, Rongping Fan, Kun Dong, Xiaoli Shi, Shujun Zhang, Xuefeng Yu & Yan Yang

  2. Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, Hubei, China

    Kun Dong, Xiaoli Shi, Shujun Zhang, Xuefeng Yu & Yan Yang

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  1. Jiaojiao Huang
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  2. Xuemin Peng
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Contributions

YY and JH conceived and designed the study and wrote the manuscript. YY, XS, KD, and XY secured the study’s funding. JH, XP, RF, KD, XS, SZ, and XY acquired and analyzed the data. All authors revised the article and approved its final version.

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Correspondence to Yan Yang.

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Huang, J., Peng, X., Fan, R. et al. Disruption of Circadian Clocks Promotes Progression of Alzheimer’s Disease in Diabetic Mice. Mol Neurobiol 58, 4404–4412 (2021). https://doi.org/10.1007/s12035-021-02425-7

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