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Research Of Experimental Periodontitis Deteriorating The Learning And Memory Function And Pathological Impairments In Alzheimer’s Disease Model Mice

Posted on:2020-05-09Degree:MasterType:Thesis
Country:ChinaCandidate:X S QianFull Text:PDF
GTID:2404330596482043Subject:Stomatology
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Objective:To observe the effect of experimental periodontitis on the learning and memory capicity of APP/PS1 transgenic mice,and further explore the possible mechanisms.Methods:Six-month-old male APP/PS1 transgenic mice were randomized divided to three groups:APP/PS1 as control group(n=10),P.g-LPS injection group(n=10),P.g-LPS injection+ligation group(n=10).P.g-LPS injection animals were injected P.g-LPS into periodontal tissue 3 times per week for 8 weeks,and P.g-LPS+ligation mice were subjected to injection and ligation the gingival sulcus of the maxillary second molar(M2)with a 4.0silk.The learning and memory function was evaluated by Morris water maze test,Y maze test and Novel object recognition test.After anesthesia,the brain,alveolar bone and gingival tissue of mouse were collected.Methylene blue staining and Micro-CT were used to observe alveolar bone loss.RT-qPCR was acess to observe pro-inflammatory cytokines(TNF-α、IL-6)mRNA expression in gingiva.The cortical and hippocampal neurons were detected by Nissl staining.The protein expressions of APP,BACE1,ADAM10,iNOS,COX-2,IL-6,TNF-α,Iba-1,GFAP,Aβ1-40,Aβ1-42-42 were examined by Western Blot.Immunohistochemistry and immunofluorescence were used to detect the activation of astrocytes and microglia,as well as the expression of Aβin the cortex and hippocampus.Results:Compared with APP/PS1 mice,alveolar bone resorption increased in the group of P.g-LPS injected and ligatured mice and the trabecular thickness,bone volume and bone volume fraction of the maxillary second molar root bifurcation area(region of interest)were significantly reduced.The expression of gingival pro-inflammatory cytokines(TNF-αand IL-6)mRNA was significantly increased in the ligation group.Mice treated with P.g-LPS and ligation displayed deteriorated cognitive impairments and the number of neurons was significantly reduced in the cortex and hippocampal CA1 and DG regions.The levels of Aβin both treated groups were also significantly higher than that in APP/PS1mice.Astrocytes and microglia cells were significantly activated,with the expression of iNOS,COX-2,IL-6 and TNF-αproteins significantly increased in the two treated groups.Furthermore,the effect of periodontitis which induced by P.g-LPS intervention concurrently increased the protein expression of APP,BACE1,Aβ1-40,Aβ1-42 and decreased the expression of ADAM10.It is worth noting that the pathological injury of mice in the P.g-LPS+Ligation group was more serious than that in the P.g-LPS injection group.Conclusions:These results demonstrated that experimental periodontitis induced by P.g-LPS with/without ligation exacerbates the learning and memory impairment of APP/PS1 mice,meanwhile deteriorates the charactically features,including augmented Aβand neuroinflammatory responses.
Keywords/Search Tags:periodontitis, Porphyromonas gingivalis lipopolysaccharide, amyloid peptide, neuroinflammation, Alzheimer’s disease
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