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Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin

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Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
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State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
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College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
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Shared-Use Research Center, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
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Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama 351-0198, Japan
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Department of Neurocognitive Science, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
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Authors to whom correspondence should be addressed.
Academic Editor: Naweed I. Syed
Cells 2021, 10(11), 3261; https://doi.org/10.3390/cells10113261
Received: 12 October 2021 / Revised: 16 November 2021 / Accepted: 19 November 2021 / Published: 22 November 2021
Alzheimer’s disease (AD), the most common form of dementia, is characterized by amyloid-β (Aβ) accumulation, microglia-associated neuroinflammation, and synaptic loss. The detailed neuropathologic characteristics in early-stage AD, however, are largely unclear. We evaluated the pathologic brain alterations in young adult App knock-in model AppNL-G-F mice at 3 and 6 months of age, which corresponds to early-stage AD. At 3 months of age, microglia expression in the cortex and hippocampus was significantly decreased. By the age of 6 months, the number and function of the microglia increased, accompanied by progressive amyloid-β deposition, synaptic dysfunction, neuroinflammation, and dysregulation of β-catenin and NF-κB signaling pathways. The neuropathologic changes were more severe in female mice than in male mice. Oral administration of dioscin, a natural product, ameliorated the neuropathologic alterations in young AppNL-G-F mice. Our findings revealed microglia-based sex-differential neuropathologic changes in a mouse model of early-stage AD and therapeutic efficacy of dioscin on the brain lesions. Dioscin may represent a potential treatment for AD. View Full-Text
Keywords: Alzheimer’s disease; AppNL-G-F; dioscin; amyloid-β; synaptic dysfunction; microglia; neuroinflammation Alzheimer’s disease; AppNL-G-F; dioscin; amyloid-β; synaptic dysfunction; microglia; neuroinflammation
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MDPI and ACS Style

Liu, X.; Zhou, Q.; Zhang, J.-H.; Wang, K.-Y.; Saito, T.; Saido, T.C.; Wang, X.; Gao, X.; Azuma, K. Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin. Cells 2021, 10, 3261. https://doi.org/10.3390/cells10113261

AMA Style

Liu X, Zhou Q, Zhang J-H, Wang K-Y, Saito T, Saido TC, Wang X, Gao X, Azuma K. Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin. Cells. 2021; 10(11):3261. https://doi.org/10.3390/cells10113261

Chicago/Turabian Style

Liu, Xiao, Qian Zhou, Jia-He Zhang, Ke-Yong Wang, Takashi Saito, Takaomi C. Saido, Xiaoying Wang, Xiumei Gao, and Kagaku Azuma. 2021. "Microglia-Based Sex-Biased Neuropathology in Early-Stage Alzheimer’s Disease Model Mice and the Potential Pharmacologic Efficacy of Dioscin" Cells 10, no. 11: 3261. https://doi.org/10.3390/cells10113261

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