Dopamine transporter imaging does not predict the number of nigral neurons in Parkinson disease

Neurology ◽  
2017 ◽  
Vol 88 (15) ◽  
pp. 1461-1467 ◽  
Author(s):  
Laura Saari ◽  
Katri Kivinen ◽  
Maria Gardberg ◽  
Juho Joutsa ◽  
Tommi Noponen ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Parkinson Disease ◽  
Dopamine Transporter ◽  
Specific Binding ◽  
Region Of Interest ◽  
Substantia Nigra Pars Compacta ◽  
Time Interval ◽  
Dat Spect ◽  
Axonal Dysfunction

Objective:To examine possible associations between in vivo brain dopamine transporter SPECT imaging and substantia nigra pars compacta (SNc) neuronal survival in Parkinson disease (PD).Methods:Nigral neuron numbers were calculated for 18 patients (11 patients with neuropathologically confirmed PD) who had been examined with dopamine transporter (DAT) SPECT before death. Correlation analyses between SNc tyrosine hydroxylase (TH)–positive and neuromelanin-containing neuron counts and DAT striatal specific binding ratios (SBRs) were performed with semiquantitative region of interest–based and voxel-based analyses.Results:Mean putamen SBR did not correlate with the number of substantia nigra TH-positive (r = −0.11, p = 0.66) or neuromelanin-containing (r = −0.07, p = 0.78) neurons. Correlations remained clearly nonsignificant when the time interval between SPECT and death was used as a covariate, when the voxel-based analysis was used, and when only patients with PD were included.Conclusions:This cohort study demonstrates that postmortem SNc neuron counts are not associated with striatal DAT binding in PD. These results fit with the theory that there is no correlation between the number of substantia nigra neurons and striatal dopamine after a certain level of damage has occurred. Striatal DAT binding in PD may reflect axonal dysfunction or DAT expression rather than the number of viable neurons.

scholarly journals Substantia nigra neuromelanin magnetic resonance imaging in patients with different subtypes of Parkinson disease

2021 ◽  
Author(s):  
Lu Wang ◽  
Yayun Yan ◽  
Liyao Zhang ◽  
Yan Liu ◽  
Ruirui Luo ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Substantia Nigra ◽  
Parkinson Disease ◽  
Clinical Symptoms ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Resonance Imaging ◽  
Mean Values

AbstractNeuromelanin (NM) is a dark pigment that mainly exists in neurons of the substantia nigra pars compacta (SNc). In Parkinson disease (PD) patients, NM concentration decreases gradually with degeneration and necrosis of dopamine neurons, suggesting potential use as a PD biomarker. We aimed to evaluate associations between NM concentration in in vivo SN and PD progression and different motor subtypes using NM magnetic resonance imaging (NM-MRI). Fifty-four patients with idiopathic PD were enrolled. Patients were divided into groups by subtypes with different clinical symptoms: tremor dominant (TD) group and postural instability and gait difficulty (PIGD) group. Fifteen healthy age-matched volunteers were enrolled as controls. All subjects underwent clinical assessment and NM-MRI examination. PD patients showed significantly decreased contrast-to-noise ratio (CNR) values in medial and lateral SN (P < 0.05) compared to controls. CNR values in lateral SN region decreased linearly with PD progression (P = 0.001). PIGD patients showed significant decreases in CNR mean values in lateral SN compared to TD patients (P = 0.004). Diagnostic accuracy of using lateral substantia nigra (SN) in TD and PIGD groups was 79% (sensitivity 76.5%, specificity 78.6%). NM concentration in PD patients decreases gradually during disease progression and differs significantly between PD subtypes. NM may be a reliable biomarker for PD severity and subtype identification.

scholarly journals Relationship between neuromelanin and dopamine terminals within the Parkinson’s nigrostriatal system

Brain ◽  
2019 ◽  
Vol 142 (7) ◽  
pp. 2023-2036 ◽  
Author(s):  
Antonio Martín-Bastida ◽  
Nicholas P Lao-Kaim ◽  
Andreas Antonios Roussakis ◽  
Graham E Searle ◽  
Yue Xing ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopamine Transporter ◽  
Substantia Nigra Pars Compacta ◽  
Control Group ◽  
Post Mortem ◽  
Significant Relationships ◽  
Affected Side

Abstract Parkinson’s disease is characterized by the progressive loss of pigmented dopaminergic neurons in the substantia nigra and associated striatal deafferentation. Neuromelanin content is thought to reflect the loss of pigmented neurons, but available data characterizing its relationship with striatal dopaminergic integrity are not comprehensive or consistent, and predominantly involve heterogeneous samples. In this cross-sectional study, we used neuromelanin-sensitive MRI and the highly specific dopamine transporter PET radioligand, 11C-PE2I, to assess the association between neuromelanin-containing cell levels in the substantia nigra pars compacta and nigrostriatal terminal density in vivo, in 30 patients with bilateral Parkinson’s disease. Fifteen healthy control subjects also underwent neuromelanin-sensitive imaging. We used a novel approach taking into account the anatomical and functional subdivision of substantia nigra into dorsal and ventral tiers and striatal nuclei into pre- and post-commissural subregions, in accordance with previous animal and post-mortem studies, and consider the clinically asymmetric disease presentation. In vivo, Parkinson’s disease subjects displayed reduced neuromelanin levels in the ventral (−30 ± 28%) and dorsal tiers (−21 ± 24%) as compared to the control group [F(1,43) = 11.95, P = 0.001]. Within the Parkinson’s disease group, nigral pigmentation was lower in the ventral tier as compared to the dorsal tier [F(1,29) = 36.19, P < 0.001] and lower in the clinically-defined most affected side [F(1,29) = 4.85, P = 0.036]. Similarly, lower dopamine transporter density was observed in the ventral tier [F(1,29) = 76.39, P < 0.001] and clinically-defined most affected side [F(1,29) = 4.21, P = 0.049]. Despite similar patterns, regression analysis showed no significant association between nigral pigmentation and nigral dopamine transporter density. However, for the clinically-defined most affected side, significant relationships were observed between pigmentation of the ventral nigral tier with striatal dopamine transporter binding in pre-commissural and post-commissural striatal subregions known to receive nigrostriatal projections from this tier, while the dorsal tier correlated with striatal projection sites in the pre-commissural striatum (P < 0.05, Benjamini-Hochberg corrected). In contrast, there were no statistically significant relationships between these two measures in the clinically-defined least affected side. These findings provide important insights into the topography of nigrostriatal neurodegeneration in Parkinson’s disease, indicating that the characteristics of disease progression may fundamentally differ across hemispheres and support post-mortem data showing asynchrony in the loss of neuromelanin-containing versus tyrosine hydroxylase positive nigral cells.

scholarly journals Dopamine transporter imaging in neurodegenerative movement disorders: PET vs. SPECT

2020 ◽  
Vol 8 (5) ◽  
pp. 349-356
Author(s):  
Vera S. Kerstens ◽  
A. Varrone
Keyword(s):  
Dopamine Transporter ◽  
Pet Imaging ◽  
Single Photon ◽  
Relevant Literature ◽  
Photon Emission ◽  
Active Role ◽  
Emission Computed Tomography ◽  
Parkinsonian Syndromes ◽  
Dat Spect

Abstract Purpose The dopamine transporter (DAT) serves as biomarker for parkinsonian syndromes. DAT can be measured in vivo with single-photon emission computed tomography (SPECT) and positron emission tomography (PET). DAT-SPECT is the current clinical molecular imaging standard. However, PET has advantages over SPECT measurements, and PET radioligands with the necessary properties for clinical applications are on the rise. Therefore, it is time to review the role of DAT imaging with SPECT compared to PET. Methods PubMed and Web of Science were searched for relevant literature of the previous 10 years. Four topics for comparison were used: diagnostic accuracy, quantitative accuracy, logistics, and flexibility. Results There are a few studies directly comparing DAT-PET and DAT-SPECT. PET and SPECT both perform well in discriminating neurodegenerative from non-neurodegenerative parkinsonism. Clinical DAT-PET imaging seems feasible only recently, thanks to simplified DAT assessments and better availability of PET radioligands and systems. The higher resolution of PET makes more comprehensive assessments of disease progression in the basal ganglia possible. Additionally, it has the possibility of multimodal target assessment. Conclusion DAT-SPECT is established for differentiating degenerative from non-degenerative parkinsonism. For further differentiation within neurodegenerative Parkinsonian syndromes, DAT-PET has essential benefits. Nowadays, because of wider availability of PET systems and radioligand production centers, and the possibility to use simplified quantification methods, DAT-PET imaging is feasible for clinical use. Therefore, DAT-PET needs to be considered for a more active role in the clinic to take a step forward to a more comprehensive understanding and assessment of Parkinson’s disease.

scholarly journals Molecular Imaging of the Dopamine Transporter

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 872 ◽  
Author(s):  
Palermo ◽  
Ceravolo
Keyword(s):  
Dopamine Transporter ◽  
Single Photon ◽  
Photon Emission ◽  
Surrogate Marker ◽  
Neuronal Loss ◽  
Drug Induced ◽  
Regulatory Changes ◽  
Quantitative Measurements ◽  
Dat Spect

Dopamine transporter (DAT) single-photon emission tomography (SPECT) with (123)Ioflupane is a widely used diagnostic tool for patients with suspected parkinsonian syndromes, as it assists with differentiating between Parkinson’s disease (PD) or atypical parkinsonisms and conditions without a presynaptic dopaminergic deficit such as essential tremor, vascular and drug-induced parkinsonisms. Recent evidence supports its utility as in vivo proof of degenerative parkinsonisms, and DAT imaging has been proposed as a potential surrogate marker for dopaminergic nigrostriatal neurons. However, the interpretation of DAT-SPECT imaging may be challenged by several factors including the loss of DAT receptor density with age and the effect of certain drugs on dopamine uptake. Furthermore, a clear, direct relationship between nigral loss and DAT decrease has been controversial so far. Striatal DAT uptake could reflect nigral neuronal loss once the loss exceeds 50%. Indeed, reduction of DAT binding seems to be already present in the prodromal stage of PD, suggesting both an early synaptic dysfunction and the activation of compensatory changes to delay the onset of symptoms. Despite a weak correlation with PD severity and progression, quantitative measurements of DAT binding at baseline could be used to predict the emergence of late-disease motor fluctuations and dyskinesias. This review addresses the possibilities and limitations of DAT-SPECT in PD and, focusing specifically on regulatory changes of DAT in surviving DA neurons, we investigate its role in diagnosis and its prognostic value for motor complications as disease progresses.

scholarly journals Pedunculopontine glutamatergic neurons control spike patterning in substantia nigra dopaminergic neurons

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Daniel J Galtieri ◽  
Chad M Estep ◽  
David L Wokosin ◽  
Stephen Traynelis ◽  
D James Surmeier
Keyword(s):  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Glutamatergic Synapses ◽  
Glutamatergic Neurons ◽  
Oscillatory Mechanisms ◽  
Goal Directed Behavior ◽  
Stimulation Of

Burst spiking in substantia nigra pars compacta (SNc) dopaminergic neurons is a key signaling event in the circuitry controlling goal-directed behavior. It is widely believed that this spiking mode depends upon an interaction between synaptic activation of N-methyl-D-aspartate receptors (NMDARs) and intrinsic oscillatory mechanisms. However, the role of specific neural networks in burst generation has not been defined. To begin filling this gap, SNc glutamatergic synapses arising from pedunculopotine nucleus (PPN) neurons were characterized using optical and electrophysiological approaches. These synapses were localized exclusively on the soma and proximal dendrites, placing them in a good location to influence spike generation. Indeed, optogenetic stimulation of PPN axons reliably evoked spiking in SNc dopaminergic neurons. Moreover, burst stimulation of PPN axons was faithfully followed, even in the presence of NMDAR antagonists. Thus, PPN-evoked burst spiking of SNc dopaminergic neurons in vivo may not only be extrinsically triggered, but extrinsically patterned as well.

scholarly journals Automatic substantia nigra segmentation in neuromelanin-sensitive MRI by deep neural network in patients with prodromal and manifest synucleinopathy

2019 ◽  
pp. S453-S458
Author(s):  
R. Krupička ◽  
S. Mareček ◽  
C. Malá ◽  
M. Lang ◽  
O. Klempíř ◽  
...  
Keyword(s):  
Neural Network ◽  
Substantia Nigra ◽  
Signal Intensity ◽  
Substantia Nigra Pars Compacta ◽  
The Neural Network ◽  
Intensity Information ◽  
Ideal Tool ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

Neuromelanin (NM) is a black pigment located in the brain in substantia nigra pars compacta (SN) and locus coeruleus. Its loss is directly connected to the loss of nerve cells in this part of the brain, which plays a role in Parkinson’s Disease. Magnetic resonance imaging (MRI) is an ideal tool to monitor the amount of NM in the brain in vivo. The aim of the study was the development of tools and methodology for the quantification of NM in a special neuromelanin-sensitive MRI images. The first approach was done by creating regions of interest, corresponding to the anatomical position of SN based on an anatomical atlas and determining signal intensity threshold. By linking the anatomical and signal intensity information, we were able to segment the SN. As a second approach, the neural network U-Net was used for the segmentation of SN. Subsequently, the volume characterizing the amount of NM in the SN region was calculated. To verify the method and the assumptions, data available from various patient groups were correlated. The main benefit of this approach is the observer-independency of quantification and facilitation of the image processing process and subsequent quantification compared to the manual approach. It is ideal for automatic processing many image sets in one batch.

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 Protective effect of Curcumin against rotenone-induced Substantia nigra pars compacta neuronal dysfunction

2021 ◽  
Author(s):  
Lilit Vahan Darbinyan ◽  
Lilia Eduard Hambardzumyan ◽  
Larisa Paylak Manukyan ◽  
Karen Vazgen Simonyan ◽  
Carlos Augusto Carvalho de Vasconcelos ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Therapeutic Agent ◽  
Male Rats ◽  
Substantia Nigra Pars Compacta ◽  
Nissl Staining ◽  
Histological Changes ◽  
Naturally Occurring ◽  
The Brain

Abstract Rotenone is involved in the degeneration of dopaminergic neurons, and curcumin may prevent or effectively slow the progression of Parkinson disease (PD). Previous research has shown that the naturally occurring phenolic compound curcumin can reduce inflammation and oxidation, making it a potential therapeutic agent for neurodegenerative diseases. The present study involves investigation of rotenone induced histological changes in the brain areas, hippocampus using Nissl staining after 35 day of subcutaneous injection administration of rotenone in adult male rats. In this study, we investigated whether curcumin protects against rotenone-induced dopaminergic neurotoxicity in a rat model by in vivo electrical recording from Substantia nigra pars compacta (SNc). Curcumin treatment significantly improved electrical activity of neurons in the SNc of rotenone-induced PD model rats. The pattern of histological alterations corresponds with electrophysiological manifestations.

Muscarine Reduces Calcium-Dependent Electrical Activity in Substantia Nigra Dopaminergic Neurons

2001 ◽  
Vol 86 (6) ◽  
pp. 2966-2972 ◽  
Author(s):  
Reese S. Scroggs ◽  
Carla G. Cardenas ◽  
Joseph A. Whittaker ◽  
Stephen T. Kitai
Keyword(s):  
Substantia Nigra ◽  
Electrical Activity ◽  
Dopaminergic Neurons ◽  
Brain Slices ◽  
Oscillatory Potentials ◽  
Substantia Nigra Pars Compacta ◽  
Pontine Nucleus ◽  
Calcium Dependent ◽  
The Brain

The effect of muscarine on Ca2+ dependent electrical activity was studied in dopamine (DA) neurons located in the substantia nigra pars compacta (SNc) in brain slices from young rats, using sharp electrodes. In most DA neurons tested, muscarine (50 μM) reduced the amplitude of spontaneous oscillatory potentials and evoked Ca2+-dependent potentials recorded in the presence of TTX. Muscarine also reduced the amplitude of the slow afterhyperpolarization (sAHP) following action potentials in most DA neurons. These data suggest that muscarine reduces Ca2+ entry in SNc DA neurons. The reduction of the amplitude of the sAHP by muscarine in DA neurons may facilitate bursting initiated by glutamatergic input by increasing the frequency at which DA neurons can fire. The reduction of the sAHP via activation of muscarinic receptors in vivo may provide a mechanism whereby cholinergic inputs to DA neurons from the tegmental peduncular pontine nucleus could modulate dopamine release at dopaminergic targets in the brain.

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