Faculty of Dentistry

Lab head: Joerg Eberhard
Location: Westmead Centre for Oral Health

Website: http://www.sydney.edu.au/dentistry

Periodontitis as a potential trigger of oxidative stress in the brain: A potential link between inflammation and depressive symptoms in older adults

Primary supervisor: Joerg Eberhard


The proposed project is based on the recent work by Duffy et al. (2015) who demonstrated an association between Glutathione concentration in the anterior cingulate cortex and depressive symptoms in a group of older adults ‘at risk’ for major depression.[1] Glutathione is the brains primary antioxidant and is considered a marker of oxidative stress. Importantly, Glutathione can be measured in-vivo using proton magnetic resonance spectroscopy (1H-MRS). As a part of the Healthy Brain Ageing imaging protocol, a 3D T1 MPRAGE sequence is also acquired, which is suitable to identify the participant’s history of periodontal diseases due to the detailed mapping of periodontal structures. Periodontitis has been identified as an independent risk factor for depression[2] and periodontal diseases are a major source of systemic oxidative stress that may also contribute to oxidative stress in the brain.[3] To combine in-vivo brain Glutathione concentration data with periodontitis experience is novel and a chance to identify a potential mechanism underpinning the relationship between chronic diseases and severe systemic health conditions such as depression. Therefore, the aim of this cross-sectional study is to investigate periodontitis as a potential source of oxidative stress in the brain, and explore how it relates to symptoms of depression in older adults.



Research methods

As described in Duffy et al (2015), a total of 58 1H-MRS scans from participants with normal or sub-threshold depressive symptoms have been previously analysed using LCModel to determine in-vivo Glutathione concentration. The corresponding 3D T1 MPRAGE scans for each participant will now be analyzed for periodontitis experience. To determine periodontitis history, bone loss will be calculated from T1 scans using ImageJ software (National Institutes of Health). Using a sagittal projection of the upper- and lower tooth rows the cemento-enamel junction of the pre-molar and molar teeth will be determined. Mesial and distal of each selected tooth the distance from the cemento-enamel junction to the crestal bone level and the tip of the root surface will be determined. This procedure will result in 2x64 data points per patients. The individual bone loss will be calculated as the mean distances from the cemento-enamel junction relative to the mean total root length in percent. Bone loss <1/3 of the root length will be classified as mild periodontitis, bone loss >1/3 of the root length as moderate to severe periodontitis. To test the association between periodontitis induced bone loss and Glutathione concentrations in the brain of those at risk and controls the Pearson correlation coefficient will be calculated. A p-value of P<0.05 will be considered as significant.



Expected outcomes

To combine data pertaining to an in-vivo marker of oxidative stress in the brain and periodontitis history is a scientific novelty, which has the potential for peer-reviewed publication. This pilot-project will demonstrate if periodontitis experience is associated with elevated Glutathione concentration in the brain of patients with depressive symptoms and adds to the current knowledge of a pathway that may represent the causal link between a chronic inflammatory process and depression, which is oxidative stress. The outcomes of this proposed project facilitate new multidisciplinary experimental research projects to provide further evidence for a link between inflammatory processes and depressive symptoms in older adults. The outcomes of this study will be used to leverage additional funding to test the generated hypotheses in clinical trials that may have a considerable impact for health care and the prevention of brain disorders through the treatment of periodontal diseases.

[1]Duffy SL, Lagopoulos J, Cockayne N, Hermens DF, Hickie IB, Naismith SL. Oxidative stress and depressive symptoms in older adults: A magnetic resonance spectroscopy study. J Affect Disord. 2015 Jul 15;180:29-35.

[2]Hsu CC, Hsu YC, Chen HJ, Lin CC, Chang KH, Lee CY, Chong LW, Kao CH. Association of Periodontitis and Subsequent Depression: A Nationwide Population-Based Study. Medicine (Baltimore). 2015 Dec;94(51):e2347.

[3]Masi S, Salpea KD, Li K, Parkar M, Nibali L, Donos N, Patel K, Taddei S, Deanfield JE, D'Aiuto F, Humphries SE. Oxidative stress, chronic inflammation, and telomere length in patients with periodontitis. Free Radic Biol Med. 2011 Mar 15;50(6):730-5.

Discipline: Applied Medical Sciences, Westmead
Co-supervisors: Shantel Duffy, Sharon Naismith
Keywords: Brain, Infection and immunity, Oral and General Health