Abstract
Background. Cardiovascular autonomic dysfunction is well known in Parkinson's disease (PD) presentation and it produces hypoperfusion of vital organs. The association between cardiovascular autonomic dysfunction and oxidative stress was examined in previous animal models. Oxidative stress and neuroinflammation were thought to have roles in PD pathogenesis. Owing to the relative low intrinsic antioxidative properties, brain white matter (WM) is vulnerable to the oxidative stress. This study is conducted to examine possible relationships by using a hypothesis-driven mediation model. Methods. Twenty-nine patients with PD and 26 healthy controls participated in this study, with complete examinations of cardiac autonomic parameters, plasma DNA level, and WM integrity. A single-level three-variable mediation model was used to investigate the possible relationships. Results. The elevated serum oxidative stress biomarkers include plasma nuclear DNA and mitochondrial DNA, and poorer cardiac autonomic parameters and multiple regional microstructural WM changes are demonstrated. Further mediation analysis shows that plasma nuclear DNA served as the mediators between poorer baroreflex sensitivity and mean diffusivity changes in cingulum. Conclusions. These results provide a possible pathophysiology for how the poor baroreflex sensitivity and higher oxidative stress adversely impacted the WM integrity. This model could provide us with a piece of the puzzle of the entire PD pathogenesis.
Highlights
Cardiovascular autonomic dysfunction is well known in Parkinson’s disease (PD) presentation and may be a leading cause of life-threatening processes [1]
We propose that (1) compared with controls PD patients show lower cardiovascular autonomic activity, higher plasma DNA levels, and poorer white matter Diffusion tensor imaging (DTI) indices; (2) associations among the reduced autonomic function, increased plasma DNA level, and reduced brain WM DTI indices existed; (3) we applied a hypothesis-driven mediation model to explore the possible interactions of autonomic dysfunction, elevated plasma DNA levels, and WM declined in PD
Our results demonstrated that the poor Baroreflex sensitivity (BRS) correlated with brain white matter microstructural deficits in PD patients
Summary
Cardiovascular autonomic dysfunction is well known in Parkinson’s disease (PD) presentation and may be a leading cause of life-threatening processes [1]. Cells suffering from a hypoxic environment in hypoperfusion tend to experience apoptosis or cell death due to impairment of the mitochondrial function [6] This process generates considerable oxidative stress and releases plasma DNA, including mitochondrial DNA and nuclear DNA, to serum. As an end result of oxidative stress, the plasma DNA level in peripheral blood could be representative of the oxidative stress status in these PD patients This provides us with an opportunity to detect possible CNS changes in peripheral blood. These results provide a possible pathophysiology for how the poor baroreflex sensitivity and higher oxidative stress adversely impacted the WM integrity. This model could provide us with a piece of the puzzle of the entire PD pathogenesis
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
