Abstract
Introduction Systemic inflammation with elevated oxidative stress causing neuroinflammation is considered a major factor in the pathogenesis of Parkinson's disease (PD). The interface between systemic circulation and the brain parenchyma is the blood-brain barrier (BBB), which also plays a role in maintaining neurovascular homeostasis. Vascular cell adhesion molecule-1 (VCAM-1) and microRNAs (miRNAs) regulate brain vessel endothelial function, neoangiogenesis, and, in turn, neuronal homeostasis regulation, such that their dysregulation can result in neurodegeneration, such as gray matter atrophy, in PD. Objective Our aim was to evaluate the associations among specific levels of gray matter atrophy, peripheral vascular adhesion molecules, miRNAs, and clinical disease severity in order to achieve a clearer understanding of PD pathogenesis. Methods Blood samples were collected from 33 patients with PD and 27 healthy volunteers, and the levels of VCAM-1 and several miRNAs in those samples were measured. Voxel-based morphometry (VBM) analysis was performed using 3 T magnetic resonance imaging (MRI) and SPM (Statistical Parametric Mapping software program). The associations among the vascular parameter, miRNAs, gray matter volume, and clinical disease severity measurements were evaluated by partial correlation analysis. Results The levels of VCAM-1, miRNA-22, and miRNA-29a expression were significantly elevated in the PD patients. The gray matter volume atrophy in the left parahippocampus, bilateral posterior cingulate gyrus, fusiform gyrus, left temporal gyrus, and cerebellum was significantly correlated with increased clinical disease severity, the upregulation of miRNA levels, and increased vascular inflammation. Conclusion Patients with PD seem to have abnormal levels of vascular inflammatory markers and miRNAs in the peripheral circulation, and these levels are correlated with specific brain volume changes. This study reinforces the associations among peripheral inflammation, the BBB interface, and gray matter atrophy in PD and further demonstrates that BBB dysfunction with neurovascular impairment may play an important role in PD progression.
Highlights
Systemic inflammation with elevated oxidative stress causing neuroinflammation is considered a major factor in the pathogenesis of Parkinson’s disease (PD)
How does this neuron damage/loss happen in the brain? Recent studies have suggested that neuroinflammation due to exogenous factors is closely related to the progression of PD [4, 5]
We identified gray matter atrophy throughout much of the cortex, including in anatomical locations that typically appear to be sensitive to the effects of inflammation, such as the cerebellum, bilateral posterior cingulate gyrus, left parahippocampus, and left temporal gyrus [30]
Summary
Systemic inflammation with elevated oxidative stress causing neuroinflammation is considered a major factor in the pathogenesis of Parkinson’s disease (PD). Our aim was to evaluate the associations among specific levels of gray matter atrophy, peripheral vascular adhesion molecules, miRNAs, and clinical disease severity in order to achieve a clearer understanding of PD pathogenesis. The associations among the vascular parameter, miRNAs, gray matter volume, and clinical disease severity measurements were evaluated by partial correlation analysis. The gray matter volume atrophy in the left parahippocampus, bilateral posterior cingulate gyrus, fusiform gyrus, left temporal gyrus, and cerebellum was significantly correlated with increased clinical disease severity, the upregulation of miRNA levels, and increased vascular inflammation. This study reinforces the associations among peripheral inflammation, the BBB interface, and gray matter atrophy in PD and further demonstrates that BBB dysfunction with neurovascular impairment may play an important role in PD progression.
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