scholarly journals Parkinson’s disease progression in the substantia nigra: location, location, location

Brain ◽  
2020 ◽  
Vol 143 (9) ◽  
pp. 2628-2630
Author(s):  
David E Vaillancourt ◽  
Trina Mitchell
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Disease Progression ◽  
Spatiotemporal Changes

This scientific commentary refers to ‘Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson’s disease’, by Biondetti et al. (doi:10.1093/brain/awaa216

scholarly journals Spatiotemporal changes in substantia nigra neuromelanin content in Parkinson’s disease

Brain ◽  
2020 ◽  
Vol 143 (9) ◽  
pp. 2757-2770 ◽  
Author(s):  
Emma Biondetti ◽  
Rahul Gaurav ◽  
Lydia Yahia-Cherif ◽  
Graziella Mangone ◽  
Nadya Pyatigorskaya ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Disease Severity ◽  
Disease Diagnosis ◽  
Signal To Noise ◽  
Control Subjects ◽  
Clinical Scores ◽  
Spatiotemporal Changes ◽  
Healthy Control

Abstract This study aimed to investigate the spatiotemporal changes in neuromelanin-sensitive MRI signal in the substantia nigra and their relation to clinical scores of disease severity in patients with early or progressing Parkinson’s disease and patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD) exempt of Parkinsonian signs compared to healthy control subjects. Longitudinal T1-weighted anatomical and neuromelanin-sensitive MRI was performed in two cohorts, including patients with iRBD, patients with early or progressing Parkinson’s disease, and control subjects. Based on the aligned substantia nigra segmentations using a study-specific brain anatomical template, parametric maps of the probability of a voxel belonging to the substantia nigra were calculated for patients with various degrees of disease severity and controls. For each voxel in the substantia nigra, probability map of controls, correlations between signal-to-noise ratios on neuromelanin-sensitive MRI in patients with iRBD and Parkinson’s disease and clinical scores of motor disability, cognition and mood/behaviour were calculated. Our results showed that in patients, compared to the healthy control subjects, the volume of the substantia nigra was progressively reduced for increasing disease severity. The neuromelanin signal changes appeared to start in the posterolateral motor areas of the substantia nigra and then progressed to more medial areas of this region. The ratio between the volume of the substantia nigra in patients with Parkinson’s disease relative to the controls was best fitted by a mono-exponential decay. Based on this model, the pre-symptomatic phase of the disease started at 5.3 years before disease diagnosis, and 23.1% of the substantia nigra volume was lost at the time of diagnosis, which was in line with previous findings using post-mortem histology of the human substantia nigra and radiotracer studies of the human striatum. Voxel-wise patterns of correlation between neuromelanin-sensitive MRI signal-to-noise ratio and motor, cognitive and mood/behavioural clinical scores were localized in distinct regions of the substantia nigra. This localization reflected the functional organization of the nigrostriatal system observed in histological and electrophysiological studies in non-human primates (motor, cognitive and mood/behavioural domains). In conclusion, neuromelanin-sensitive MRI enabled us to assess voxel-wise modifications of substantia nigra’s morphology in vivo in humans, including healthy controls, patients with iRBD and patients with Parkinson’s disease, and identify their correlation with nigral function across all motor, cognitive and behavioural domains. This insight could help assess disease progression in drug trials of disease modification.

scholarly journals Voltage-Gated Ca2+ Channels in Dopaminergic Substantia Nigra Neurons: Therapeutic Targets for Neuroprotection in Parkinson's Disease?

2021 ◽  
Vol 13 ◽  
Author(s):  
Nadine J. Ortner
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Disease Progression ◽  
Therapeutic Potential ◽  
Oxidant Stress ◽  
Substantia Nigra Pars Compacta ◽  
Pacemaker Activity ◽  
Channel Blockers ◽  
Voltage Gated

The loss of dopamine (DA)-producing neurons in the substantia nigra pars compacta (SN) underlies the core motor symptoms of the progressive movement disorder Parkinson's disease (PD). To date, no treatment to prevent or slow SN DA neurodegeneration exists; thus, the identification of the underlying factors contributing to the high vulnerability of these neurons represents the basis for the development of novel therapies. Disrupted Ca2+ homeostasis and mitochondrial dysfunction seem to be key players in the pathophysiology of PD. The autonomous pacemaker activity of SN DA neurons, in combination with low cytosolic Ca2+ buffering, leads to large somatodendritic fluctuations of intracellular Ca2+ levels that are linked to elevated mitochondrial oxidant stress. L-type voltage-gated Ca2+ channels (LTCCs) contribute to these Ca2+ oscillations in dendrites, and LTCC inhibition was beneficial in cellular and in vivo animal models of PD. However, in a recently completed phase 3 clinical trial, the dihydropyridine (DHP) LTCC inhibitor isradipine failed to slow disease progression in early PD patients, questioning the feasibility of DHPs for PD therapy. Novel evidence also suggests that R- and T-type Ca2+ channels (RTCCs and TTCCs, respectively) represent potential PD drug targets. This short review aims to (re)evaluate the therapeutic potential of LTCC, RTCC, and TTCC inhibition in light of novel preclinical and clinical data and the feasibility of available Ca2+ channel blockers to modify PD disease progression. I also summarize their cell-specific roles for SN DA neuron function and describe how their gating properties allow activity (and thus their contribution to stressful Ca2+ oscillations) during pacemaking.

Preventive treatments to slow substantia nigra damage and Parkinson’s disease progression: A critical perspective review

2020 ◽  
Vol 161 ◽  
pp. 105065 ◽  
Author(s):  
Geir Bjørklund ◽  
Maryam Dadar ◽  
George Anderson ◽  
Salvatore Chirumbolo ◽  
Michael Maes
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Disease Progression ◽  
Critical Perspective

scholarly journals 123-I ioflupane (Datscan®) presynaptic nigrostriatal imaging in patients with movement disorders

2005 ◽  
Vol 48 (spe2) ◽  
pp. 115-126 ◽  
Author(s):  
Angel Soriano Castrejón ◽  
Ana María García Vicente ◽  
Montserrat Cortés Romera ◽  
Julia Vaamonde Cano ◽  
Sonia Rodado Marina ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Movement Disorder ◽  
Essential Tremor ◽  
Disease Progression ◽  
Movement Disorders ◽  
Neurodegenerative Disorders ◽  
Nigrostriatal Pathway

123-I Ioflupane (Datscan®) presynaptic imaging has been shown to have a significant utility in the assessment of patients with movement disorders 123-I Ioflupane SPECT is able to distinguish between Parkinson’s disease (PD) and other forms of parkinsonism without degeneration of the nigrostriatal pathway, including a common movement disorder such as essential tremor, and to assess disease progression in PD and other neurodegenerative disorders involving the substantia nigra.

scholarly journals Substantia Nigra Neuromelanin as an Imaging Biomarker of Disease Progression in Parkinson’s Disease

2017 ◽  
Vol 7 (3) ◽  
pp. 491-501 ◽  
Author(s):  
Margherita Fabbri ◽  
Sofia Reimão ◽  
Miguel Carvalho ◽  
Rita G. Nunes ◽  
Daisy Abreu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Disease Progression ◽  
Imaging Biomarker

Hyperechogenicity of substantia nigra in Parkinson's disease – Searching for genetic predictors

2008 ◽  
Vol 35 (S 01) ◽  
Author(s):  
C Funke ◽  
A Soehn ◽  
C Schulte ◽  
M Bonin ◽  
C Klein ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Genetic Predictors
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