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Article type: Research Article
Authors: Duan, Lian | Qian, Xueshen | Wang, Qin | Huang, Lan | Ge, Song; *
Affiliations: Hospital of Stomatology, Zunyi Medical University, Zunyi, Guizhou, China
Correspondence: [*] Correspondence to: Song Ge, Hospital of Stomatology, Zunyi Medical University, Zunyi, Guizhou, 563000, China. Tel.: +86 851 2863 5717; E-mail: [email protected].
Abstract: Background:With advancements in periodontal medicine, the relationship between periodontitis and systemic diseases has garnered increasing attention. Recently, emerging evidence has indicated that periodontitis may be involved in the pathogenesis of Alzheimer’s disease (AD). Objective:To assess the impact of experimental periodontitis on cognitive function deficits in a rat model of streptozotocin-induced AD and determine the mechanisms underlying these effects. Methods:Rats were randomly assigned to the control (C), experimental periodontitis (P), Alzheimer’s disease (AD), and experimental periodontitis with streptozotocin-induced AD (AD-P) groups. Experimental periodontitis was induced using ligation and coating with Porphyromonas gingivalis. In the AD-P group, AD was induced by intracerebroventricular injection of streptozotocin after 6 weeks of experimental periodontitis induction. Results:Compared with the group C rats, those in group P exhibited alveolar bone resorption, learning and memory function impairment, and decreased insulin sensitivity and insulin signaling-related protein expression. Glial cell activation and cognitive impairment in streptozotocin-induced groups with significantly increased phosphorylated tau levels were more pronounced relative to the C group. The number of neurons and insulin sensitivity and insulin signaling-related protein expression in group AD-P rats were lower than those in the AD alone group, while the expressions of glial fibrillary acidic protein, tau phosphorylation, interleukin-6, and cyclooxygenase-2 were significantly increased. Conclusion:Periodontitis may be a risk factor exacerbating cognitive deficits in an AD-like neurodegenerative context, possibly by impairing the insulin signaling pathway and stimulating gliosis and neuroinflammation.
Keywords: Alzheimer’s disease, insulin sensitivity, insulin signaling pathway, periodontitis, streptozotocin
DOI: 10.3233/JAD-215720
Journal: Journal of Alzheimer's Disease, vol. 88, no. 1, pp. 57-74, 2022
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