ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Neurocognitive Aging and Behavior
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1628520
This article is part of the Research TopicTherapeutic Target for Alzheimer's Disease – Innate Immunity in Both CNS and PeripheryView all 4 articles
Tooth Loss Impairs Cognitive Function in SAMP8 Mice by aggravating pyroptosis of microglia via the cGAS/STING Pathway
Provisionally accepted
- Beijing Stomatological Hospital, Capital Medical University, Beijing, China
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Alzheimer's Disease (AD) is a common neurodegenerative disease among the elderly population. It has been posited that the onset and progression of AD is influenced by a combination of various factors. Occlusal support loss due to tooth loss has been reported to be a risk factor triggering cognitive dysfunction. This study aimed to investigate the relationship between tooth loss and cognitive dysfunction and illustrate the role of pyroptosis in advancing Alzheimer's disease. Here, we report that 5-month-old male SAMP8 mice, a model of accelerated aging, experienced cognitive decline and exhibited impaired spatial memory in the Y-maze and Novel Object Recognition (NOR) tests following the loss of bilateral upper molars. The pathological section staining revealed an upregulation of GSDMD, a target protein of pyroptosis, and abnormal activation of the cGAS/STING pathway, particularly in microglia, after tooth loss. Subsequently, we further validated the close link between the cGAS/STING pathway and pyroptosis. In vitro, we demonstrated that the BV2 microglia knockdown STING group improved the inflammatory cascade response and down-regulated the pyroptotic features. Collectively, these data suggest that the occlusal support loss due to tooth loss induces pyroptosis-related protein deposition, which may be intimately associated with the cGAS/STING signaling pathway.
Keywords: Alzheimer's disease, cognitive dysfunction, Tooth Loss, cGAS/STING, GSDMD, SAMP8
Received: 14 May 2025; Accepted: 29 Jul 2025.
Copyright: © 2025 Sun, Lu, HU, Meng, Wang and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: QingSong Jiang, Beijing Stomatological Hospital, Capital Medical University, Beijing, China
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