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Grant number: 22/02050-4
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2022
Effective date (End): July 31, 2023
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Elaine Aparecida Del Bel Belluz Guimarães
Grantee:Gabrielle Jacob
Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


Changes in the upper and lower gastrointestinal tract microbiome have been documented in Parkinson's disease (PD). The oral microbiota is scarcely studied in this context, despite its fundamental role in maintaining oral and systemic health and the evidence that Parkinsonian individuals have a higher prevalence of periodontitis. Although there is intercommunication between the periodontal microbiome and the inflammatory response of the host, a causal relationship between the two is not yet known. Despite this, there is evidence of an interconnection between the inflammatory reaction induced by periodontitis and the central and peripheral nervous system. The hypothesis of this study is that immune responses induced by periodontitis can alter the production and release of inflammatory cytokines, important triggers of glial reactivity in the nervous system and, as a consequence, the potentiation of the degenerative process. To test this hypothesis, the effects of sustained periodontal inflammation on the susceptibility to injury/neurodegeneration of dopaminergic neurons and its consequences will be investigated in an experimental model of PD. The pro-inflammatory environment would also favor the increase of glial cells and the production of reactive oxygen species (ROS), the latter accelerating dopaminergic neuronal death in this animal model. To induce periodontal disease in rats, a ligature will be placed around the lower first molars. Dopaminergic neuronal injury with the neurotoxin 6-hydroxydopamine microinjected into the right medial forebrain bundle will be used for PD induction. Alveolar bone loss and periodontal inflammation will be analyzed by microcomputed tomography, histomorphometric and immunohistochemical analyzes of periodontal tissues. The analysis will be performed by immunohistochemistry of the enzyme tyrosine hydroxylase, by markers of glial cells and by fluorometry of reactive oxygen species. The effect of periodontitis on PD motor signs will be investigated by the walk test. In order to evaluate the effect of periodontitis on the development of the parkinsonian lesion, as well as on the already established lesion, two experimental protocols are proposed: (i) Induction of periodontitis 1 week before the induction of the parkinsonian lesion; (ii) induction of periodontitis 1 week after induction of the parkinsonian lesion. The suggested proposition of periodontal therapy influencing neurodegenerative disease may help to elucidate several aspects related to periodontal inflammation and neuroinflammation in PD.

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