Systemic Administration of Lipopolysaccharide Decreased Expression of Neprilysin in Mouse

Objectives: Increasing evidence suggests that Periodontal diseases are involved in the pathogenesis of Alzheimer’s disease, and an association between periodontitis and amyloid-β(Aβ) deposition in the elderly was demonstrated. Neprilysin functions as an Aβ degrading enzyme, downregulation of neprilysin expression may have caused increased Aβ deposition. The aim of this study was to examine the effects of systemic administration of Porphyromonas gingivalis-derived lipopolysaccharide (PG-LPS) on neprilysin expression in the hippocampus of adult and senescence-accelerated mice.
Methods: PG-LPS was intraperitoneally administered to male C57BL/6J and senescence-accelerated mouse prone 8 (SAMP8) at a dose of 5 mg/kg every 3 days for a duration of 3 months. The expression levels of neprilysin and IL-10 mRNAs were evaluated by quantitative RT-PCR. The protein level of neprilysin was observed by westen blot using anti-neprilysin antibody (56C6, Abcam,UK). Sections obtained from brain tissue were immunohistochemically stained with an anti-neprilysin antibody as a primary antibody. Data were compared between groups using the Mann Whitney U test and Kruskal–Wallis test followed by the Holm method. A p value < 0.05 was considered to indicate statistically significant results.
Results: The expression of IL-10 mRNA was significantly upregulated by the stimulation with LPS in SAMP8 (p<0.01). In SAMP8, neprilysin expression at both the mRNA and protein levels was significantly lower in the PG-LPS group than in the control group (p < 0.05). The immunofluorescence intensity of neprilysin in the CA3 region of the hippocampus was significantly lower in PG-LPS-treated mice than in control mice (p < 0.01)
Conclusions: In the present study, we demonstrated that systemic administration of PG-LPS induced downregulation of neprilysin expression in SAMP8 senescence-accelerated mice. P. gingivalis-induced downregulation of neprilysin expression may be involved in increased Aβ deposition in the elderly.