The impact of ligature‐induced periodontitis on an experimental mouse model of Alzheimer’s disease

Abstract

Background: Alzheimer’s disease (AD) is the most common form of dementia characterized by the presence of amyloid plaques, neurofibrillary tangles and the activation of the brain immune system. Studies from the public health have shown that activation of the immune cells in the periphery can lead to neuroimmune responses, which can initiate or perpetuate neurodegenerative brain changes that underlie cognitive impairment. One of the common sources of chronic systemic inflammation is periodontitis, which is an inflammatory disease that destroys gums and teeth. We hypothesize that periodontal bone loss due to periodontitis gums may intensify the neuroimmune responses in AD and exacerbate the disease conditions. Method: A 5-0 silk ligature was placed around the maxillary upper second molars in female 3xTg mice for 5 weeks to induce periodontal bone loss. Open field test was performed to assess the sickness behavior; Spontaneous Y maze and puzzle box test were used to assess the cognitive functions of the mice. Following behavioral testing, the upper maxillary jaws were dissected out and subjected to histological analysis to examine periodontal bone loss. Different brain regions were harvested for biochemical analysis. Result: After 5 weeks, ligature-induced periodontitis led to a significant loss of periodontal bone level in 3xTg mice. It also induced inflammation in the hippocampus and frontal cortex regions. A significant reduction of exploratory motivation was also observed in ligated AD mice compared to WT control. No impairment of short-term memory was observed in ligated AD mice, but they exhibited significant reduction in the total arm entries, which is also an indicator of a reduction in exploratory behavior. In the puzzle box test, ligature-induced periodontitis induced long-term memory impairment in ligated AD mice Conclusion: Altogether, ligature-induced periodontitis led to increase neuroimmune responses in the brains of AD mice, a reduction of exploratory motivation as well as long term memory impairment. As bone loss induced by ligation led to increased neuroinflammation. Future work will aim to elucidate the mechanism of how periodontal bone loss and the cytokine innate response lead to neuroimmune response. Acknowledgement: The study is supported by Health and Medical Research Fund (HMRF 04151216) to RCCC.