Abstract
Low levels of the natural antioxidant uric acid (UA) and the presence of REM sleep behavior disorder (RBD) are both associated with an increased likelihood of developing Parkinson's disease (PD). RBD and PD are also accompanied by basal ganglia dysfunction including decreased nigrostriatal and nigrocortical resting state functional connectivity. Despite these independent findings, the relationship between UA and substantia nigra (SN) functional connectivity remains unknown. In the present study, voxelwise analysis of covariance was used in a cross-sectional design to explore the relationship between UA and whole-brain SN functional connectivity using the eyes-open resting state fMRI method in controls without RBD, patients with idiopathic RBD, and PD patients with and without RBD. The results showed that controls exhibited a positive relationship between UA and SN functional connectivity with left lingual gyrus. The positive relationship was reduced in patients with RBD and PD with RBD, and the relationship was found to be negative in PD patients. These results are the first to show differential relationships between UA and SN functional connectivity among controls, prodromal, and diagnosed PD patients in a ventral occipital region previously documented to be metabolically and structurally altered in RBD and PD. More investigation, including replication in longitudinal designs with larger samples, is needed to understand the pathophysiological significance of these changes.
Highlights
Parkinson’s disease (PD) is a chronic, progressive neurologic disease characterized by motor deficits that include tremor at rest, rigidity, slowing of movement, and postural instability
An analysis of variance (ANOVA) showed no main effect of group on uric acid (UA) levels [F(3, 64) = 1.789, p = 0.158, R2 = 0.077]
If the hypothesis that REM sleep behavior disorder (RBD) is a prodromal state of PD, with idiopathic RBD a kind of intermediate state between controls and PD, the pattern of slopes found with controls highest and positive, RBD in between, and PD lowest and negative may be consistent with more neurodegeneration from RBD to PD corresponding to reduced functional connectivity
Summary
Parkinson’s disease (PD) is a chronic, progressive neurologic disease characterized by motor deficits that include tremor at rest, rigidity, slowing of movement, and postural instability. Etiologic factors include a role for aging [1], a role for environmental factors [2, 3] including herbicide/pesticide exposure, and specific disease-causing genetic mutations, most notably in the α-synuclein [4], and the parkin [5] genes. The free radical-mediated injury theory, which is referred to as the oxidant stress hypothesis, is arguably the leading explanation for pathogenesis due most notably to the fact that the major degradative pathway for dopamine is its oxidative deamination by monoamine oxidase A and B resulting in highly reactive hydroxyl radicals [6]. Since oxidative stress appears to play a role in the pathogenesis of Parkinson’s disease (PD) [9, 10], questions remain about the role of antioxidants in PD and especially during the prodromal stage
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
