Correction: Brain iron deposition is linked with cognitive severity in Parkinson’s disease

Background: Brain iron deposition, low hemoglobin (HGB), and increased heme oxygenase-1 (HO-1) have been implicated in Parkinson’s disease (PD). However, the association among them in PD is poorly studied.Objective: To explore the association of the level of HO-1 with brain iron deposition and low level of HGB in PD.Methods: A total of 32 patients with PD and 26 controls were recruited for this study. C57BL/6 male mice were used in generating 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced chronic PD model. The Levels of serum HO-1 and HGB of human subjects and mice were assayed by ELISA, blood routine test, respectively. Quantitative susceptibility mapping (QSM) was used to quantitatively analyze brain iron deposition in human subjects and mice. HO-1 inhibitor (Sn-protoporphyrin, SnPP) was used to suppress the function and expression of HO-1 in PD mice. Correlations between the concentration of serum HO-1 and iron deposition of the region of interests (ROIs), levels of HGB, between the three factors mentioned above, and scores of clinical scales were explored in PD patients.Results: This study revealed significant elevation of the serum HO-1 concentration, iron deposition within bilateral substantial nigra (SN), red nucleus (RN), and putamen (PUT) and decrease of HGB level in PD patients. There was a significantly positive correlation between the serum HO-1 concentration and iron deposition within SN, an inverse correlation between the serum HO-1 concentration and HGB level in PD patients. A significant increase in HO-1 expression of serum and iron deposition in SN was also observed in the PD mouse model, and the SnPP could significantly reduce iron deposition in the SN.Conclusions: The high level of HO-1 may be the common mechanism of iron deposition and low HGB in PD. Therefore, the findings presented in this study indicate that HO-1 correlates with brain iron deposition and anemia in PD.

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Relationship Between Brain Iron Deposition and Mitochondrial Dysfunction in Idiopathic Parkinson’s Disease

10.21203/rs.3.rs-929923/v1 ◽

2021 ◽

Author(s):

Jannik Prasuhn ◽

Martin Göttlich ◽

Friederike Gerkan ◽

Sofia Kourou ◽

Britt Ebeling ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mitochondrial Dysfunction ◽

Globus Pallidus ◽

Iron Deposition ◽

Idiopathic Parkinson’S Disease ◽

Brain Iron ◽

Idiopathic Parkinson's Disease ◽

Brain Iron Deposition

Abstract BackgroundThe underlying pathophysiology of Parkinson's disease is complex, involving different molecular pathways, including brain iron deposition and mitochondrial dysfunction. At a molecular level, these disease mechanisms are likely interconnected. Therefore, they offer potential strategies for disease-modifying treatments. We aimed to investigate subcortical brain iron deposition as a potential predictor of the bioenergetic status in patients with idiopathic Parkinson’s disease. MethodsThirty patients with idiopathic Parkinson's disease underwent multimodal MR imaging (T1, susceptibility-weighted imaging, SWI) and 31Phosphorus Magnetic Resonance Spectroscopy Imaging. Contrast-to-noise ratios based on the SWI images of the putamen, caudate, globus pallidus, and thalamus for each hemisphere were used in a multiple linear regression model to predict in vivo metabolites. ResultsSubcortical brain iron deposition, particularly in the putamen and globus pallidus, was highly predictive of the region-specific amount of high-energy-containing phosphorus metabolites in our subjects. ConclusionsOur study suggests that brain iron deposition but not the variability of individual volumetric measurements are highly predictive of mitochondrial impairment in vivo. These findings offer the opportunity, e.g., by using chelating therapies, to improve mitochondrial bioenergetics in patients with idiopathic Parkinson's disease.

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Brain iron deposition in Parkinson's disease imaged using the PRIME magnetic resonance sequence

Brain ◽

10.1093/brain/123.12.2423 ◽

2000 ◽

Vol 123 (12) ◽

pp. 2423-2431 ◽

Cited By ~ 155

Author(s):

J. M. Graham

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Magnetic Resonance ◽

Iron Deposition ◽

Brain Iron ◽

Magnetic Resonance Sequence ◽

Brain Iron Deposition

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Brain iron deposition fingerprints in Parkinson's disease and progressive supranuclear palsy

Movement Disorders ◽

10.1002/mds.24926 ◽

2012 ◽

Vol 27 (3) ◽

pp. 421-427 ◽

Cited By ~ 46

Author(s):

Kai Boelmans ◽

Brigitte Holst ◽

Marc Hackius ◽

Jürgen Finsterbusch ◽

Christian Gerloff ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Progressive Supranuclear Palsy ◽

Iron Deposition ◽

Brain Iron ◽

Brain Iron Deposition

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Regional brain iron and gene expression provide insights into neurodegeneration in Parkinson’s disease

Brain ◽

10.1093/brain/awab084 ◽

2021 ◽

Author(s):

George E C Thomas ◽

Angeliki Zarkali ◽

Mina Ryten ◽

Karin Shmueli ◽

Ana Luisa Gil Martinez ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Expression Profiles ◽

Nervous System Development ◽

Synaptic Function ◽

Iron Accumulation ◽

Iron Deposition ◽

Brain Atlas ◽

Biological Processes ◽

Brain Iron

Abstract The mechanisms which are responsible for the selective vulnerability of specific neuronal populations in Parkinson’s disease are poorly understood. Oxidative stress secondary to brain iron accumulation is one postulated mechanism. We measured iron deposition in 180 cortical regions in 96 patients with Parkinson’s disease and 35 controls using quantitative susceptibility mapping. We estimated the expression of 15 745 genes in the same regions using transcriptomic data from the Allen Human Brain Atlas. Using partial least squares regression, we then identified the profile of gene transcription in the healthy brain that underlies increased cortical iron in patients with Parkinson’s disease relative to controls. With gene ontological tools, we investigated the biological processes and cell types associated with this transcriptomic profile. We identified the sets of genes whose spatial expression profiles in control brains correlated significantly with the spatial pattern of cortical iron deposition in Parkinson’s disease. Gene ontological analyses revealed that these genes were enriched for biological processes relating to heavy metal detoxification, synaptic function and nervous system development and were predominantly expressed in astrocytes and glutamatergic neurons. We also show that genes found to be differentially expressed in Parkinson’s disease play a role in explaining the pattern of cortical expression we identified. Our findings provide mechanistic insights into regional selective vulnerabilities in Parkinson’s disease, particularly into processes involving iron accumulation.

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