Abstract
We used forebrain-specific conditional presenilin 1 (PS1) and presenilin 2 (PS2) double knockout mice (dKO mice) that exhibit symptoms of neurodegenerative diseases, especially Alzheimer’s disease, to investigate whether ibuprofen can rescue brain and periodontal tissue abnormalities by attenuating the inflammatory response. Mandibles were dissected for alveolar bone-height analysis. Maxillae were fixed and decalcified for histological observation and osteoclast detection. ELISA measurements from the hippocampus, cortex, and gingiva of the mandibular incisor teeth were used to assay inflammatory mediators. We confirmed periodontal tissue abnormalities and inflammatory responses in brain and periodontal tissues in naive nine- and 12-month-old dKO mice. The other two groups of age-matched dKO mice that received 375-ppm ibuprofen treatment for six consecutive months exhibited significantly attenuated damage in periodontal tissues and reduction in several inflammation-related factors in brain and periodontal tissues. Our findings showed that the anti-inflammatory drug ibuprofen significantly decreased inflammation through the cyclooxygenase (COX) pathway in brain and periodontal tissues in dKO mice, and then attenuated abnormalities in periodontal tissues. This suggests that ibuprofen could be an ideal drug for preventing both nervous system and periodontal tissue damage caused by inflammatory responses.
Highlights
Presenilin mutations are linked to more than 90% of early onset familial Alzheimer’s disease (AD)cases [1]
Since no mice received oral care treatment in this study, our results indicate that inflammatory response is the most likely cause of the periodontal tissue abnormalities found in dKO mice
We found that ibuprofen alleviated the abnormalities in periodontal tissues: the number of inflammatory cells in the periodontal ligament was less and the cementum layer was consistent and regular (Figure 3), and alveolar bone loss was significantly less at 12 months (Figure 1C)
Summary
Presenilin mutations are linked to more than 90% of early onset familial Alzheimer’s disease (AD). Leukocyte serum levels were reported to be elevated beginning at six months, and cytokine and chemokine levels, such as those of TNF-α and IL-1β, were significantly higher both in brain and serum at nine months These findings indicate that a robust inflammatory response appears early in the brains of dKO mice and expands to the periphery [7]. The number of osteoclasts and amount of alveolar bone loss significantly increased at nine months, periodontal tissues showed obvious histomorphological abnormalities, and inflammatory mediators—such as TNF-α and IL-1β—increased in gingiva with age. These data indicate that inflammation in dKO mice brains can expand to the periphery and lead to abnormalities in periodontal tissues [19]. This allows us to discuss potential therapeutic methods that might attenuate abnormalities in the brain and periodontal tissues
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