Exploring the Potential Impact of Periodontitis on the Induction or Development of Parkinson’S Disease: Utilizing Platelet Lysate as a Possible Therapeutic Strategy( I )

Periodontitis is one of the most prevalent chronic inflammatory diseases, which affects the supporting tissues of the teeth. Numerous periodontal pathogens and their endotoxin (mainly lipopolysaccharide, LPS) may enter the systemic circulation through the oral ulcerations in periodontal pocket, and induce the pro-inflammatory cytokine production (such as IL-1β, IL-6, and TNF-) that causes systemically inflammation not only to local tissue but also to a variety of visceral organs. This increased inflammatory burden forms the basis for the proposed link between periodontitis and various systemic diseases such as cardiac diseases, diabetes, renal diseases, low birth weight as well as Alzheimer disease. Parkinson’s disease is a chronic progressive neurodegenerative disorder in which persisted inflammatory reaction in dopaminergic neurons of the substantia nigra (SN) may contribute to the aetiology and pathogenesis of this disease. Previous studies have indicated that intra-ventricular injection of LPS could induce strong microglial activation and enhanced pro-inflammatory cytokine levels, which selectively leads to the neurodegeneration of dopaminergic neurons. Pharmacological results also demonstrated that subjects on regular anti-inflammatory drugs have a reduced risk of Parkinson’s disease, which further highlights the importance of inflammatory reaction in initiation and progression of this disorder. However, although chronic inflammation is consistently associated with the pathophysiology of Parkinson’s disease, so far, there is no direct evidence implicating the effect of periodontitis in the pathogenesis of Parkinson’s disease. Therefore, the aim of the present project is to (1) Clarify the potential impact of periodontitis on the induction of Parkinson’s disease through both in vitro and in vivo analysis. For the in vitro study, by exposing the LUHMES cell (the midbrain dopaminergic cell) to periodontal pathogens-derived LPS, we can understand the cellular responses as well as the signaling pathway involved in the periodontitis-induced Parkinson’s disease. For the in vivo study, the pathological change as well as the related neurochemical expressions in the SN could be extensively determined by employing two animal models of directly injecting the periodontal pathogens-derived LPS to periodontium and tightly encompassing the periodontium with cotton threads. [First year] (2) Investigate whether platelet lysate that exerts powerful anti-inflammatory and anti-bacterial effects could serve as a significant therapeutic strategy to counteract the neurological deficits originated from periodontitis-induced Parkinson’s disease. [Second year] With the smooth processing of this project, we hope that the link between periodontitis and Parkinson’s disease could be successfully established. If this is true, an attempt can be made to prevent or improve the clinical symptoms of Parkinson’s disease just by simply emphasizing the oral hygiene or applying the platelet lysate therapy.