Investigations of differences in iron oxidation state inside single neurons from substantia nigra of Parkinson’s disease and control patients using the micro-XANES technique

Abstract Background Dopaminergic (DA) neurons of the substantia nigra pars compacta (SNpc) selectively and progressively degenerate in Parkinson’s disease (PD). Until now, molecular analyses of DA neurons in PD have been limited to genomic and transcriptomic approaches, whereas, to the best of our knowledge, no proteomic or combined polyomic study examining the protein profile of these neurons, is currently available. Methods In this exploratory study, we used laser microdissection to extract DA neurons from 10 human SNpc samples obtained at autopsy in PD patients and control subjects. Extracted RNA and proteins were identified by RNA sequencing and nano-LC-MS/MS, respectively, and the differential expression between the PD and control group was assessed. Results Qualitative analyses confirmed that the microdissection protocol preserves the integrity of our samples and offers access to specific molecular pathways. This polyomic analysis highlighted differential expression of 52 genes and 33 proteins, including molecules of interest already known to be dysregulated in PD, such as LRP2, PNMT, CXCR4, MAOA and CBLN1 genes, or the Aldehyde dehydrogenase 1 protein. On the other hand, despite the same samples were used for both analyses, correlation between RNA and protein expression was low, as exemplified by the CST3 gene encoding for the cystatin C protein. Conclusion This is the first exploratory study analyzing both gene and protein expression of LMD-dissected DA neurons from SNpc in PD. Although correlation between RNA and protein expressions was limited, this polyomic study provides an extensive and integrated overview of molecular changes identified in the PD SNpc and may offer novel insights into specific pathological processes at work in PD degeneration.

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Dopamine transporter messenger RNA in Parkinson's disease and control substantia nigra neurons

Annals of Neurology ◽

10.1002/ana.410350421 ◽

1994 ◽

Vol 35 (4) ◽

pp. 494-498 ◽

Cited By ~ 99

Author(s):

George R. Uhl ◽

Donna Walther ◽

Deborah Mash ◽

Baptiste Faucheux ◽

France Javoy-Agid

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Dopamine Transporter ◽

Messenger Rna ◽

And Control

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Multiomic Analyses of Dopaminergic Neurons Isolated from Human Substantia Nigra in Parkinson’s Disease: A Descriptive and Exploratory Study

Cellular and Molecular Neurobiology ◽

10.1007/s10571-021-01146-8 ◽

2021 ◽

Author(s):

Affif Zaccaria ◽

Paola Antinori ◽

Virginie Licker ◽

Enikö Kövari ◽

Johannes A. Lobrinus ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Protein Expression ◽

Differential Expression ◽

Dopaminergic Neurons ◽

Exploratory Study ◽

Control Group ◽

Gene And Protein Expression ◽

And Control

AbstractDopaminergic neurons (DA) of the substantia nigra pars compacta (SNpc) selectively and progressively degenerate in Parkinson’s disease (PD). Until now, molecular analyses of DA in PD have been limited to genomic or transcriptomic approaches, whereas, to the best of our knowledge, no proteomic or combined multiomic study examining the protein profile of these neurons is currently available. In this exploratory study, we used laser capture microdissection to extract regions from DA in 10 human SNpc obtained at autopsy in PD patients and control subjects. Extracted RNA and proteins were identified by RNA sequencing and nanoliquid chromatography–mass spectrometry, respectively, and the differential expression between PD and control group was assessed. Qualitative analyses confirmed that the microdissection protocol preserves the integrity of our samples and offers access to specific molecular pathways. This multiomic analysis highlighted differential expression of 52 genes and 33 proteins, including molecules of interest already known to be dysregulated in PD, such as LRP2, PNMT, CXCR4, MAOA and CBLN1 genes, or the Aldehyde dehydrogenase 1 protein. On the other hand, despite the same samples were used for both analyses, correlation between RNA and protein expression was low, as exemplified by the CST3 gene encoding for the cystatin C protein. This is the first exploratory study analyzing both gene and protein expression of laser-dissected neuronal parts from SNpc in PD. Data are available via ProteomeXchange with identifier PXD024748 and via GEO with identifier GSE 169755.

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T1 and T2 Relaxation Times from Substantia Nigra in Parkinson's Disease and Control

Acta Physica Polonica A ◽

10.12693/aphyspola.125.869 ◽

2014 ◽

Vol 125 (4) ◽

pp. 869-871

Author(s):

R. Kuliński ◽

K. Szlachta ◽

J. Gałązka-Friedman ◽

A. Friedman

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Relaxation Times ◽

T2 Relaxation ◽

T1 And T2 ◽

And Control

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Regional Metal Concentrations in Parkinson's Disease, Other Chronic Neurological Diseases, and Control Brains

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100029140 ◽

1989 ◽

Vol 16 (3) ◽

pp. 310-314 ◽

Cited By ~ 85

Author(s):

Ryan J. Uitti ◽

A.H. Rajput ◽

B. Rozdilsky ◽

M. Bickis ◽

T. Wollin ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Caudate Nucleus ◽

Neurological Diseases ◽

Neurofibrillary Tangle ◽

Atomic Emission ◽

Brain Regions ◽

Metal Concentrations ◽

And Control

ABSTRACT:Metal deficiency or toxicity states have been recognized as a cause of several neurological disorders and are suspected in others. We analyzed four brain regions (frontal cortex, caudate nucleus, substantia nigra, and cerebellum) in 36 human brains for concentrations of 24 metals (Ag, Al, As, B, Be, Ca, Cd, Co, Cr, Cu, Fe, K, Pb, Mg, Mn, Mo, Na, Ni, P, Se, Ti, V, W, Zn). Regional metal concentrations, measured using atomic absorption and atomic emission spectroscopy, were compared between 9 Parkinson's disease (PD) brains, 15 brains from patients with other chronic neurological diseases, and 12 control brains. No significant metal concentration differences were noted between brains from PD and other chronic neurologic disease. However, parkinsonian brains (PD and parkinsonism secondary to neurofibrillary tangle disease) showed lower concentrations of magnesium in the caudate nucleus and copper in the substantia nigra than control brains. These findings may represent an etiologically important clue to parkinsonism.

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Different Signals of Magnetic Resonance Imaging and Ultrasound from Substantia Nigra in Parkinson's Disease and Control - Is Iron the Cause?

Acta Physica Polonica A ◽

10.12693/aphyspola.121.454 ◽

2012 ◽

Vol 121 (2) ◽

pp. 454-456 ◽

Cited By ~ 2

Author(s):

K. Szlachta ◽

K. Sadowski ◽

R. Kuliński ◽

J. Gałązka-Friedman ◽

A. Friedman

Keyword(s):

Magnetic Resonance Imaging ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Magnetic Resonance ◽

Substantia Nigra ◽

Resonance Imaging ◽

And Control

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Polyomic analyses of dopaminergic neurons isolated from human substantia nigra in Parkinson’s disease: An exploratory study.

10.21203/rs.3.rs-182873/v2 ◽

2021 ◽

Author(s):

Affif ZACCARIA ◽

Paola Antinori Malaspina ◽

Virginie Licker ◽

Enikö Kovari ◽

Johannes A Lobrinus ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Substantia Nigra ◽

Protein Expression ◽

Differential Expression ◽

Dopaminergic Neurons ◽

Exploratory Study ◽

Substantia Nigra Pars Compacta ◽

Gene And Protein Expression ◽

And Control

Abstract Dopaminergic neurons of the substantia nigra pars compacta selectively and progressively degenerate in Parkinson’s disease. Until now, molecular analyses of dopaminergic neurons in PD have been limited to genomic and transcriptomic approaches, whereas, to the best of our knowledge, no proteomic or combined polyomic study examining the protein profile of these neurons, is currently available. In this exploratory study, we used laser microdissection to extract dopaminergic neurons from 10 human SNpc samples obtained at autopsy in Parkinson’s disease patients and control subjects. Extracted RNA and proteins were identified by RNA sequencing and nano-LC-MS/MS, respectively, and the differential expression between Parkinson’s disease and control group was assessed. Qualitative analyses confirmed that the microdissection protocol preserves the integrity of our samples and offers access to specific molecular pathways. This polyomic analysis highlighted differential expression of 52 genes and 33 proteins, including molecules of interest already known to be dysregulated in Parkinson’s disease, such as LRP2 , PNMT , CXCR4 , MAOA and CBLN1 genes, or the Aldehyde dehydrogenase 1 protein. On the other hand, despite the same samples were used for both analyses, correlation between RNA and protein expression was low, as exemplified by the CST3 gene encoding for the cystatin C protein. This is the first exploratory study analyzing both gene and protein expression of LMD-dissected neurons from substantia nigra pars compacta in Parkinson’s disease. Data are available via ProteomeXchange with identifier PXD024748 and via GEO with identifier GSE 169755.

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