scholarly journals Synaptic Density and Neuronal Metabolic Function Measured by Positron Emission Tomography in the Unilateral 6-OHDA Rat Model of Parkinson’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Nakul Ravi Raval ◽  
Frederik Gudmundsen ◽  
Morten Juhl ◽  
Ida Vang Andersen ◽  
Nikolaj Speth ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Positron Emission Tomography ◽  
Parkinson's Disease ◽  
Emission Tomography ◽  
Metabolic Function ◽  
Synaptic Density ◽  
Fdg Uptake ◽  
Ventral Midbrain ◽  
Positron Emission ◽  
Cortical Regions

Parkinson’s disease (PD) is caused by progressive neurodegeneration and characterised by motor dysfunction. Neurodegeneration of dopaminergic neurons also causes aberrations within the cortico-striato-thalamo-cortical (CSTC) circuit, which has been hypothesised to lead to non-motor symptoms such as depression. Individuals with PD have both lower synaptic density and changes in neuronal metabolic function in the basal ganglia, as measured using [11C]UCB-J and [18F]FDG positron emission tomography (PET), respectively. However, the two radioligands have not been directly compared in the same PD subject or in neurodegeneration animal models. Here, we investigate [11C]UCB-J binding and [18F]FDG uptake in the CSTC circuit following a unilateral dopaminergic lesion in rats and compare it to sham lesioned rats. Rats received either a unilateral injection of 6-hydroxydopamine (6-OHDA) or saline in the medial forebrain bundle and rostral substantia nigra (n = 4/group). After 3 weeks, all rats underwent two PET scans using [18F]FDG, followed by [11C]UCB-J on a separate day. [18F]FDG uptake and [11C]UCB-J binding were both lower in the ipsilateral striatal regions compared to the contralateral regions. Using [11C]UCB-J, we could detect an 8.7% decrease in the ipsilateral ventral midbrain, compared to a 2.9% decrease in ventral midbrain using [18F]FDG. Differential changes between hemispheres for [11C]UCB-J and [18F]FDG outcomes were also evident in the CSTC circuit’s cortical regions, especially in the orbitofrontal cortex and medial prefrontal cortex where higher synaptic density yet lower neuronal metabolic function was observed, following lesioning. In conclusion, [11C]UCB-J and [18F]FDG PET can detect divergent changes following a dopaminergic lesion in rats, especially in cortical regions that are not directly affected by the neurotoxin. These results suggest that combined [11C]UCB-J and [18F]FDG scans could yield a better picture of the heterogeneous cerebral changes in neurodegenerative disorders.

scholarly journals Synaptic density and neuronal metabolic function measured by PET in the unilateral 6-OHDA rat model of Parkinson's disease

2021 ◽  
Author(s):  
Nakul Ravi Raval ◽  
Frederik Gudmundsen ◽  
Morten Juhl ◽  
Ida Nymann Petersen ◽  
Annesofie Videbæk ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Dysfunction ◽  
Metabolic Function ◽  
Synaptic Density ◽  
Fdg Uptake ◽  
Positron Emission ◽  
Progressive Neurodegeneration ◽  
Cortical Regions ◽  
6 Hydroxydopamine

Parkinson's disease (PD) is caused by progressive neurodegeneration and characterised by motor dysfunction. Neurodegeneration of dopaminergic neurons also causes aberrations within the cortico-striato-thalamo-cortical (CSTC) circuit, which has been hypothesised to lead to non-motor symptoms such as depression. Individuals with PD have both lower synaptic density and changes in neuronal metabolic function in the basal ganglia, as measured using [11C]UCB-J and [18F]FDG positron emission tomography (PET), respectively. However, the two radioligands have not been directly compared in the same PD subject or in neurodegeneration animal models. Here, we investigate [11C]UCB-J binding and [18F]FDG uptake in the CSTC circuit following a unilateral dopaminergic lesion in rats and compare it to sham lesioned rats. Rats received either a unilateral injection of 6-hydroxydopamine (6-OHDA) or saline in the medial forebrain bundle and rostral substantia nigra (n=4/group). After three weeks, all rats underwent two PET scans using [18F]FDG, followed by [11C]UCB-J on a separate day. While [18F]FDG uptake and [11C]UCB-J binding were both lower in the ipsilateral striatal regions compared to the contralateral regions, we found a larger difference in the ipsilateral striatum (8.9%) and ventral midbrain (8.7%) for [11C]UCB-J, compared to [18F]FDG (5.7% and 2.9% respectively). Differential changes between hemispheres for [11C]UCB-J and [18F]FDG outcomes were also evident in the CSTC circuit's cortical regions, especially in the orbitofrontal cortex and medial prefrontal cortex where higher synaptic density yet lower neuronal metabolic function was observed, following lesioning. In conclusion, [11C]UCB-J and [18F]FDG PET can detect divergent changes following a dopaminergic lesion in rats, especially in cortical regions that are not directly affected by the neurotoxin. These results suggest that combined [11C]UCB-J and [18F]FDG scan could yield a better picture of the heterogeneous cerebral changes in neurodegenerative disorders.

scholarly journals Observation of magnetic susceptibility changes within the thalamus: a comparative study between healthy and Parkinson’s disease afflicted cynomolgus monkeys using 7 T MRI

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Sangwoo Kim ◽  
Youngjeon Lee ◽  
Chang-Yeop Jeon ◽  
Yeung Bae Jin ◽  
Sukhoon Oh ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Parkinson’S Disease ◽  
Positron Emission Tomography ◽  
Parkinson's Disease ◽  
Magnetic Resonance ◽  
Disease Model ◽  
Emission Tomography ◽  
Resonance Imaging ◽  
Cynomolgus Monkeys ◽  
Positron Emission

Abstract Background Although the thalamus is known to modulate basal ganglia function related to motor control activity, the abnormal changes within the thalamus during distinct medical complications have been scarcely investigated. In order to explore the feasibility of assessing iron accumulation in the thalamus as an informative biomarker for Parkinson’s disease (PD), this study was designed to employ quantitative susceptibility mapping using a 7 T magnetic resonance imaging system in cynomolgus monkeys. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-injected cynomolgus monkey and a healthy control (HC) were examined by 7 T magnetic resonance imaging. Positron emission tomography with 18F-N-(3-fluoro propyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane was also employed to identify the relationship between iron deposits and dopamine depletion. All acquired values were averaged within the volume of interest of the nigrostriatal pathway. Findings Compared with the HC, the overall elevation of iron deposition within the thalamus in the Parkinson’s disease model (about 53.81% increase) was similar to that in the substantia nigra (54.81%) region. Substantial susceptibility changes were observed in the intralaminar part of the thalamus (about 70.78% increase). Additionally, we observed that in the Parkinson’s disease model, binding potential values obtained from positron emission tomography were considerably decreased in the thalamus (97.51%) and substantia nigra (92.48%). Conclusions The increased iron deposition in the thalamus showed negative correlation with dopaminergic activity in PD, supporting the idea that iron accumulation affects glutaminergic inputs and dopaminergic neurons. This investigation indicates that the remarkable susceptibility changes in the thalamus could be an initial major diagnostic biomarker for Parkinson’s disease-related motor symptoms.

Analysis of SCA2 and SCA3/MJD repeats in Parkinson's disease in mainland China: Genetic, clinical, and positron emission tomography findings

2009 ◽  
Vol 24 (13) ◽  
pp. 2007-2011 ◽  
Author(s):  
Jun-Ling Wang ◽  
Bin Xiao ◽  
Xiang-Xiang Cui ◽  
Ji-Feng Guo ◽  
Li-Fang Lei ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Positron Emission Tomography ◽  
Parkinson's Disease ◽  
Mainland China ◽  
Emission Tomography ◽  
Positron Emission
Sign in / Sign up

Export Citation Format

Share Document