Altered Striatocerebellar Metabolism and Systemic Inflammation in Parkinson’s Disease
Altered Striatocerebellar Metabolism and Systemic Inflammation in Parkinson’s Disease
Chiun-Chieh Yu,1 Meng-Hsiang Chen,1 Cheng-Hsien Lu,2 Yung-Cheng Huang,3 Hsiu-Ling Chen,1 Nai-Wen Tsai,2 Hung-Chen Wang,4 I-Hsiao Yang,1 Shau-Hsuan Li,5 and Wei-Che Lin1
1Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83305, Taiwan
2Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83305, Taiwan
3Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83305, Taiwan
4Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83305, Taiwan
5Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83305, Taiwan
Received 4 February 2016; Revised 24 June 2016; Accepted 25 July 2016
Academic Editor: Ravinder K. Kaundal
Copyright © 2016 Chiun-Chieh Yu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Parkinson’s disease (PD) is the most second common neurodegenerative movement disorder. Neuroinflammation due to systemic inflammation and elevated oxidative stress is considered a major factor promoting the pathogenesis of PD, but the relationship of structural brain imaging parameters to clinical inflammatory markers has not been well studied. Our aim was to evaluate the association of magnetic resonance spectroscopy (MRS) measures with inflammatory markers. Blood samples were collected from 33 patients with newly diagnosed PD and 30 healthy volunteers. MRS data including levels of N-acetylaspartate (NAA), creatine (Cre), and choline (Cho) were measured in the bilateral basal ganglia and cerebellum. Inflammatory markers included plasma nuclear DNA, plasma mitochondrial DNA, and apoptotic leukocyte levels. The Cho/Cre ratio in the dominant basal ganglion, the dominant basal ganglia to cerebellum ratios of two MRS parameters NAA/Cre and Cho/Cre, and levels of nuclear DNA, mitochondrial DNA, and apoptotic leukocytes were significantly different between PD patients and normal healthy volunteers. Significant positive correlations were noted between MRS measures and inflammatory marker levels. In conclusion, patients with PD seem to have abnormal levels of inflammatory markers in the peripheral circulation and deficits in MRS measures in the dominant basal ganglion and cerebellum.
1. Introduction
Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease and has been characterized as a progressive neurological disorder without any available cure or preventative treatment [1, 2]. The etiology of PD remains uncertain. Genetic and exogenous factors (such as aging, environmental factors, and oxidative stress) and their interaction play key roles in PD pathogenesis [1, 3]. Neuroinflammation has been considered to be closely related to the progression of PD [4]. Elevated oxidative stress and mitochondrial involvement may trigger neuroinflammation [5, 6], thereby activating microglia and astrocytes and facilitating subsequent infiltration of the blood brain barrier (BBB) by peripheral immune cells [7, 8]. Imbalance in cellular homeostasis leads to different forms of programmed neuron cell death including apoptosis and necrosis [9–11]. Moreover, previous studies show leukocyte apoptosis is significantly higher in PD patients and associated with central dopamine neuron loss [12]. Demonstration of an association between peripheral and central inflammation might help clarify the pathogenesis of PD.
Proton (1H) magnetic resonance spectroscopy (MRS) can be used to noninvasively monitor changes in brain metabolite levels in PD patients, and methods of detecting levels of specific hydrogen-containing compounds in vivo can be used to measure neuron cell integrity and brain energy metabolism in PD patients [13]. Metabolites measured by 1H-MRS include N-acetylaspartate (NAA; a marker of neuronal integrity), choline-containing compounds (Cho; a marker of membrane turnover and glial proliferation), and creatine with phosphocreatine (Cre; a marker of tissue energetic metabolism, usually considered an internal control). MRS is widely used to monitor brain areas including the basal ganglia, substantia nigra, temporoparietal cortex, prefrontal cortex, posterior cingulated cortex, pontine basis, and occipital lobe [13–15] and as a diagnostic tool for differentiating PD from other neurodegenerative diseases [16]. Recently, it has been demonstrated that PD’s effect on the striatopallidal circuit and cerebellothalamocortical circuit is responsible for many clinical features [17, (...truncated)