Dataset Information

Ventral posterior substantia nigra iron increases over 3 years in Parkinson's disease.

ABSTRACT:

Background

Parkinson's disease (PD) is characterized in part by the progressive accumulation of iron within the substantia nigra (SN); however, its spatial and temporal dynamics remain relatively poorly understood.

Objectives

The objective of this study was to investigate spatial patterns and temporal evolution of SN iron accumulation in PD.

Methods

A total of 18 PD patients (mean disease duration = 6.2 years) receiving dopaminergic therapy and 16 healthy controls were scanned with 3T MRI at baseline and 3 years later using quantitative susceptibility mapping, an indirect marker of iron content. Iron was assessed separately in the posterior SN and anterior SN at the ventral and dorsal levels of the SN. The results were corrected for the false discovery rate.

Results

A significant group effect was found for the ventral posterior SN (P < .001) and anterior SN (P = .042) quantitative susceptibility mapping as well as significant group x time interaction effects (P = .02 and P = .043, respectively). In addition, a significant intragroup change during 3 years of follow-up was found only in the ventral posterior SN of PD (P = .012), but not healthy controls. No significant effects were detected for any dorsal SN measures. No associations were identified with clinical measures.

Conclusions

We found both cross-sectional and longitudinal SN iron changes to be confined to its more ventral location in PD. Because pathology studies also show the ventral SN to degenerate early and to the greatest extent in PD, the assessment of iron levels by quantitative susceptibility mapping in this area may potentially represent a disease progression biomarker in PD. © 2019 International Parkinson and Movement Disorder Society.

SUBMITTER: Bergsland N

PROVIDER: S-EPMC6642003 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Ventral posterior substantia nigra iron increases over 3 years in Parkinson's disease.

Bergsland Niels N Zivadinov Robert R Schweser Ferdinand F Hagemeier Jesper J Lichter David D Guttuso Thomas T

Movement disorders : official journal of the Movement Disorder Society 20190610 7

<h4>Background</h4>Parkinson's disease (PD) is characterized in part by the progressive accumulation of iron within the substantia nigra (SN); however, its spatial and temporal dynamics remain relatively poorly understood.<h4>Objectives</h4>The objective of this study was to investigate spatial patterns and temporal evolution of SN iron accumulation in PD.<h4>Methods</h4>A total of 18 PD patients (mean disease duration = 6.2 years) receiving dopaminergic therapy and 16 healthy controls were scan ...[more]

PMID: 31180615

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Project description:BackgroundParkinson's disease (PD) is the most common neurodegenerative disorder involving the motor system. Although not being the only region involved in PD, affection of the substantia nigra and its projections is responsible for some of the most debilitating features of the disease. To further advance a comprehensive understanding of nigral pathology, we conducted a tissue based comparative proteome study of healthy and diseased human substantia nigra.ResultsThe gross number of differentially regulated proteins in PD was 221. In total, we identified 37 proteins, of which 16 were differentially expressed. Identified differential proteins comprised elements of iron metabolism (H-ferritin) and glutathione-related redox metabolism (GST M3, GST P1, GST O1), including novel redox proteins (SH3BGRL). Additionally, many glial or related proteins were found to be differentially regulated in PD (GFAP, GMFB, galectin-1, sorcin), as well as proteins belonging to metabolic pathways sparsely described in PD, such as adenosyl homocysteinase (methylation), aldehyde dehydrogenase 1 and cellular retinol-binding protein 1 (aldehyde metabolism). Further differentially regulated proteins included annexin V, beta-tubulin cofactor A, coactosin-like protein and V-type ATPase subunit 1. Proteins that were similarly expressed in healthy or diseased substantia nigra comprised housekeeping proteins such as COX5A, Rho GDI alpha, actin gamma 1, creatin-kinase B, lactate dehydrogenase B, disulfide isomerase ER-60, Rab GDI beta, methyl glyoxalase 1 (AGE metabolism) and glutamine synthetase. Interestingly, also DJ-1 and UCH-L1 were expressed similarly. Furthermore, proteins believed to serve as internal standards were found to be expressed in a constant manner, such as 14-3-3 epsilon and hCRMP-2, thus lending further validity to our results.ConclusionUsing an approach encompassing high sensitivity and high resolution, we show that alterations of SN in PD include many more proteins than previously thought. The results point towards a heterogeneous aetiopathogenesis of the disease, including alterations of GSH-related proteins as well as alterations of proteins involved in retinoid metabolism, and they indicate that proteins involved in familial PD may not be differentially regulated in idiopathic Parkinson's disease.

Project description:Substantia nigra (SN) hyperechogenicity is present in most Parkinson's disease (PD) cases but is occasionally absent in some. To date, age, gender, disease severity, and other factors have been reported to be associated with SN hyperechogenicity in PD. Previous studies have discovered that excess iron deposition in the SN underlies its hyperechogenicity in PD, which may also indicate the involvement of genes associated with iron metabolism in hyperechogenicity. The objective of our study is to explore the potential associations between variants in iron metabolism-associated genes and SN echogenicity in Han Chinese PD. Demographic profiles, clinical data, SN echogenicity and genotypes were obtained from 221 Han Chinese PD individuals with a sufficient bone window. Serum ferritin levels were quantified in 92 of these individuals by immunochemical assay. We then compared factors between PD individuals with SN hyperechogenicity and those with SN hypoechogenicity to identify factors that predispose to SN hyperechogenicity. Of our 221 participants, 122 (55.2%) displayed SN hyperechogenicity, and 99 (44.8%) displayed SN hypoechogenicity. Gender and serum ferritin levels were found to be associated with SN hyperechogenicity. In total, 14 genes were included in the sequencing part. After data processing, 34 common single nucleotide polymorphisms were included in our further analyses. In our data, we also found a significantly higher frequency of PANK2 rs3737084 (genotype: OR = 2.07, P = 0.013; allele: OR = 2.51, P = 0.002) in the SN hyperechogenic group and a higher frequency of PLA2G6 rs731821 (genotype: OR = 0.45, P = 0.016; allele: OR = 0.44, P = 0.011) in the SN hypoechogenic group. However, neither of the two variants was found to be correlated with serum ferritin. This study demonstrated that genetic factors, serum ferritin level, and gender may explain the interindividual variability in SN echogenicity in PD. This is an explorative study, and further replication is warranted in larger samples and different populations.

Dataset Information

Ventral posterior substantia nigra iron increases over 3 years in Parkinson's disease.

Background

Objectives

Methods

Results

Conclusions

Publications

Ventral posterior substantia nigra iron increases over 3 years in Parkinson's disease.

Similar Datasets

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