scholarly journals Microstructural Abnormalities of Substantia Nigra in Parkinson’s disease: A Neuromelanin Sensitive MRI Atlas Based Study

2019 ◽  
Author(s):  
Apoorva Safai ◽  
Shweta Prasad ◽  
Jitender Saini ◽  
Pramod Kumar Pal ◽  
Madhura Ingalhalikar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Diffusion Tensor ◽  
Region Of Interest ◽  
Substantia Nigra Pars Compacta ◽  
Microstructural Changes ◽  
Severity Scores ◽  
Mri Sequences ◽  
The Right

AbstractMicrostructural changes associated with degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNc) in Parkinson’s disease (PD) have been studied using Diffusion Tensor Imaging (DTI). However, these studies show inconsistent results, mainly due to methodological variations in delineation of SNc. To mitigate this, our work aims to construct a probabilistic atlas of SNc based on a Neuromelanin sensitive MRI (NMS-MRI) sequence and demonstrate its applicability to investigate microstructural changes on a large dataset of PD. Using manual segmentation and deformable registrations, we create a novel SNc atlas in the MNI space using NMS-MRI sequences of 27 healthy controls (HC). We employ this atlas to evaluate the diffusivity and anisotropy measures, derived from diffusion MRI in the SNc of 135 patients with PD and 99 HCs. Our observations of significantly increased diffusivity measures provide evidence of microstructural abnormalities in PD. However, no changes in the anisotropy were observed. Moreover, the asymmetry in abnormalities is prominent as the left SNc showed significant increase in diffusivity, and a reduction in FA when compared to the right SNc. Further the diffusivity and FA values also demonstrated a trend when correlated with the PD severity scores. Overall, from this work we establish a normative baseline for the SNc region of interest using NMS-MRI while the application on PD data emphasizes on the contribution of diffusivity measures rather than anisotropy of white matter in PD.

scholarly journals Automated Assessment of the Substantia Nigra Pars Compacta in Parkinson’s Disease: A Diffusion Tensor Imaging Study

2021 ◽  
Vol 11 (11) ◽  
pp. 1235
Author(s):  
Niels Bergsland ◽  
Laura Pelizzari ◽  
Maria Marcella Laganá ◽  
Sonia Di Tella ◽  
Federica Rossetto ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Diffusion Tensor Imaging ◽  
Substantia Nigra ◽  
Rating Scale ◽  
Diffusion Tensor ◽  
Imaging Study ◽  
Substantia Nigra Pars Compacta ◽  
Disease Rating ◽  
Magnetic Resonance Imaging Mri

The substantia nigra (SN) pars compacta (SNpc) and pars reticulata (SNpr) are differentially affected in Parkinson’s disease (PD). Separating the SNpc and SNpr is challenging with standard magnetic resonance imaging (MRI). Diffusion tensor imaging (DTI) allows for the characterization of SN microstructure in a non-invasive manner. In this study, 29 PD patients and 28 healthy controls (HCs) were imaged with 1.5T MRI for DTI. Images were nonlinearly registered to standard space and SNpc and SNpr DTI parameters were measured. ANCOVA and receiver operator characteristic (ROC) analyses were performed. Clinical associations were assessed with Spearman correlations. Multiple corrections were controlled for false discovery rate. PD patients presented with significantly increased SNpc axial diffusivity (AD) (1.207 ± 0.068 versus 1.156 ± 0.045, p = 0.024), with ROC analysis yielding an under the curve of 0.736. Trends with Unified Parkinson’s Disease Rating Scale (UPDRS) III scores were identified for SNpc MD (rs = 0.449), AD (rs = 0.388), and radial diffusivity (rs = 0.391) (all p < 0.1). A trend between baseline SNpr MD and H&Y change (rs = 0.563, p = 0.081) over 2.9 years of follow-up was identified (n = 14). In conclusion, SN microstructure shows robust, clinically meaningful associations in PD.

scholarly journals Proteomic Characterization of Synaptosomes from Human Substantia Nigra Indicates Altered Mitochondrial Translation in Parkinson’s Disease

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2580
Author(s):  
Sarah Plum ◽  
Britta Eggers ◽  
Stefan Helling ◽  
Markus Stepath ◽  
Carsten Theiss ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Gradient Centrifugation ◽  
Synaptic Function ◽  
Substantia Nigra Pars Compacta ◽  
Differential Analysis ◽  
Mitochondrial Translation ◽  
Control Subjects ◽  
Core Proteome

The pathological hallmark of Parkinson’s disease (PD) is the loss of neuromelanin-containing dopaminergic neurons within the substantia nigra pars compacta (SNpc). Additionally, numerous studies indicate an altered synaptic function during disease progression. To gain new insights into the molecular processes underlying the alteration of synaptic function in PD, a proteomic study was performed. Therefore, synaptosomes were isolated by density gradient centrifugation from SNpc tissue of individuals at advanced PD stages (N = 5) as well as control subjects free of pathology (N = 5) followed by mass spectrometry-based analysis. In total, 362 proteins were identified and assigned to the synaptosomal core proteome. This core proteome comprised all proteins expressed within the synapses without regard to data analysis software, gender, age, or disease. The differential analysis between control subjects and PD cases revealed that CD9 antigen was overrepresented and fourteen proteins, among them Thymidine kinase 2 (TK2), mitochondrial, 39S ribosomal protein L37, neurolysin, and Methionine-tRNA ligase (MARS2) were underrepresented in PD suggesting an alteration in mitochondrial translation within synaptosomes.

Loss of insulin receptor immunoreactivity from the substantia nigra pars compacta neurons in Parkinson's disease

1994 ◽  
Vol 87 (4) ◽  
pp. 343-348
Author(s):  
I. Moroo ◽  
T. Yamada ◽  
H. Makino ◽  
I. Tooyama ◽  
P. L. McGeer ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Insulin Receptor ◽  
Substantia Nigra Pars Compacta

Neurofilament mRNA is reduced in Parkinson's disease substantia nigra pars compacta neurons

1993 ◽  
Vol 329 (3) ◽  
pp. 328-336 ◽  
Author(s):  
William D. Hill ◽  
Motomi Arai ◽  
Jeffrey A. Cohen ◽  
John Q. Trojanowski
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Substantia Nigra Pars Compacta

scholarly journals Diffusion Kurtosis Imaging of Substantia Nigra Is a Sensitive Method for Early Diagnosis and Disease Evaluation in Parkinson’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Guohua Zhang ◽  
Yuhu Zhang ◽  
Chengguo Zhang ◽  
Yukai Wang ◽  
Guixian Ma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Rating Scale ◽  
Diffusion Tensor ◽  
Diffusion Kurtosis Imaging ◽  
Healthy Controls ◽  
Potential Biomarker ◽  
Diffusion Kurtosis ◽  
Sensitive Method

Background.To diagnose Parkinson disease (PD) in an early stage and accurately evaluate severity, it is important to develop a sensitive method for detecting structural changes in the substantia nigra (SN).Method.Seventy-two untreated patients with early PD and 72 healthy controls underwent diffusion tensor and diffusion kurtosis imaging. Regions of interest were drawn in the rostral, middle, and caudal SN by two blinded and independent raters. Mean kurtosis (MK) and fractional anisotropy in the SN were compared between the groups. Receiver operating characteristic (ROC) and Spearman correlation analyses were used to compare the diagnostic accuracy and correlate imaging findings with Hoehn-Yahr (H-Y) staging and part III of the Unified Parkinson’s Disease Rating Scale (UPDRS-III).Result.MK in the SN was increased significantly in PD patients compared with healthy controls. The area under the ROC curve was 0.976 for MK in the SN (sensitivity, 0.944; specificity, 0.917). MK in the SN had a positive correlation with H-Y staging and UPDRS-III scores.Conclusion.Diffusion kurtosis imaging is a sensitive method for PD diagnosis and severity evaluation. MK in the SN is a potential biomarker for imaging studies of early PD that can be widely used in clinic.

scholarly journals Polyomic Analyses of Dopaminergic Neurons Isolated From Human Substantia Nigra in Parkinson’s Disease: An Exploratory Study.

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 ◽  
Exploratory Study ◽  
Substantia Nigra Pars Compacta ◽  
Control Group ◽  
Gene And Protein Expression ◽  
And Control

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.

scholarly journals Correcting differential gene expression analysis for cyto-architectural alterations in substantia nigra of Parkinson's disease patients reveals known and potential novel disease-associated genes and pathways

2021 ◽  
Author(s):  
Federico Ferraro ◽  
Christina Fevga ◽  
Vincenzo Bonifati ◽  
Wim Mandemakers ◽  
Ahmed Mahfouz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Expression Profiles ◽  
Meta Analysis ◽  
Gene Expression Profiles ◽  
Substantia Nigra Pars Compacta ◽  
Ammonium Transport ◽  
Protein Interaction Data

Several studies have analyzed gene expression profiles in the substantia nigra to better understand the pathological mechanisms causing Parkinson's disease (PD). However, the concordance between the identified gene signatures in these individual studies was generally low. This might be caused by a change in cell type composition as loss of dopaminergic neurons in the substantia nigra pars compacta is a hallmark of PD. Through an extensive meta-analysis of nine previously published microarray studies, we demonstrated that a big proportion of the detected differentially expressed genes was indeed caused by cyto-architectural alterations due to the heterogeneity in the neurodegenerative stage and/or technical artifacts. After correcting for cell composition, we identified a common signature that deregulated the previously unreported ammonium transport, as well as known biological processes including bioenergetic pathways, response to proteotoxic stress, and immune response. By integrating with protein-interaction data, we shortlisted a set of key genes, such as LRRK2, PINK1, and PRKN known to be related to PD; others with compelling evidence for their role in neurodegeneration, such as GSK3β, WWOX, and VPC; as well as novel potential players in the PD pathogenesis, including NTRK1, TRIM25, ELAVL1. Together, these data showed the importance of accounting for cyto-architecture in these analyses and highlight the contribution of multiple cell types and novel processes to PD pathology providing potential new targets for drug development.

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