Synaptic Density and Neuronal Metabolic Function Measured by Positron Emission Tomography in the Unilateral 6-OHDA Rat Model of Parkinson’s Disease
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...
Guardado en:
| Autores principales: | , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/208306ca073a449cbd98aebf8b4617c7 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:208306ca073a449cbd98aebf8b4617c7 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:208306ca073a449cbd98aebf8b4617c72021-11-18T05:10:58ZSynaptic Density and Neuronal Metabolic Function Measured by Positron Emission Tomography in the Unilateral 6-OHDA Rat Model of Parkinson’s Disease1663-356310.3389/fnsyn.2021.715811https://doaj.org/article/208306ca073a449cbd98aebf8b4617c72021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnsyn.2021.715811/fullhttps://doaj.org/toc/1663-3563Parkinson’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.Nakul Ravi RavalNakul Ravi RavalFrederik GudmundsenMorten JuhlIda Vang AndersenIda Vang AndersenNikolaj SpethAnnesofie VidebækIda Nymann PetersenJens D. MikkelsenJens D. MikkelsenPatrick MacDonald FisherMatthias Manfred HerthMatthias Manfred HerthPontus Plavén-SigrayGitte Moos KnudsenGitte Moos KnudsenMikael PalnerMikael PalnerMikael PalnerFrontiers Media S.A.articleParkinson’s disease (PD)dopamine neurodegeneration6-OHDA = 6-hydroxydopamineCSTC = cortico-striato-thalamo-corticalFDG – PETSV2ANeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Synaptic Neuroscience, Vol 13 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Parkinson’s disease (PD) dopamine neurodegeneration 6-OHDA = 6-hydroxydopamine CSTC = cortico-striato-thalamo-cortical FDG – PET SV2A Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 |
| spellingShingle |
Parkinson’s disease (PD) dopamine neurodegeneration 6-OHDA = 6-hydroxydopamine CSTC = cortico-striato-thalamo-cortical FDG – PET SV2A Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Nakul Ravi Raval Nakul Ravi Raval Frederik Gudmundsen Morten Juhl Ida Vang Andersen Ida Vang Andersen Nikolaj Speth Annesofie Videbæk Ida Nymann Petersen Jens D. Mikkelsen Jens D. Mikkelsen Patrick MacDonald Fisher Matthias Manfred Herth Matthias Manfred Herth Pontus Plavén-Sigray Gitte Moos Knudsen Gitte Moos Knudsen Mikael Palner Mikael Palner Mikael Palner Synaptic Density and Neuronal Metabolic Function Measured by Positron Emission Tomography in the Unilateral 6-OHDA Rat Model of Parkinson’s Disease |
| description |
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. |
| format |
article |
| author |
Nakul Ravi Raval Nakul Ravi Raval Frederik Gudmundsen Morten Juhl Ida Vang Andersen Ida Vang Andersen Nikolaj Speth Annesofie Videbæk Ida Nymann Petersen Jens D. Mikkelsen Jens D. Mikkelsen Patrick MacDonald Fisher Matthias Manfred Herth Matthias Manfred Herth Pontus Plavén-Sigray Gitte Moos Knudsen Gitte Moos Knudsen Mikael Palner Mikael Palner Mikael Palner |
| author_facet |
Nakul Ravi Raval Nakul Ravi Raval Frederik Gudmundsen Morten Juhl Ida Vang Andersen Ida Vang Andersen Nikolaj Speth Annesofie Videbæk Ida Nymann Petersen Jens D. Mikkelsen Jens D. Mikkelsen Patrick MacDonald Fisher Matthias Manfred Herth Matthias Manfred Herth Pontus Plavén-Sigray Gitte Moos Knudsen Gitte Moos Knudsen Mikael Palner Mikael Palner Mikael Palner |
| author_sort |
Nakul Ravi Raval |
| title |
Synaptic Density and Neuronal Metabolic Function Measured by Positron Emission Tomography in the Unilateral 6-OHDA Rat Model of Parkinson’s Disease |
| title_short |
Synaptic Density and Neuronal Metabolic Function Measured by Positron Emission Tomography in the Unilateral 6-OHDA Rat Model of Parkinson’s Disease |
| title_full |
Synaptic Density and Neuronal Metabolic Function Measured by Positron Emission Tomography in the Unilateral 6-OHDA Rat Model of Parkinson’s Disease |
| title_fullStr |
Synaptic Density and Neuronal Metabolic Function Measured by Positron Emission Tomography in the Unilateral 6-OHDA Rat Model of Parkinson’s Disease |
| title_full_unstemmed |
Synaptic Density and Neuronal Metabolic Function Measured by Positron Emission Tomography in the Unilateral 6-OHDA Rat Model of Parkinson’s Disease |
| title_sort |
synaptic density and neuronal metabolic function measured by positron emission tomography in the unilateral 6-ohda rat model of parkinson’s disease |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/208306ca073a449cbd98aebf8b4617c7 |
| work_keys_str_mv |
AT nakulraviraval synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT nakulraviraval synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT frederikgudmundsen synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT mortenjuhl synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT idavangandersen synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT idavangandersen synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT nikolajspeth synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT annesofievidebæk synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT idanymannpetersen synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT jensdmikkelsen synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT jensdmikkelsen synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT patrickmacdonaldfisher synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT matthiasmanfredherth synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT matthiasmanfredherth synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT pontusplavensigray synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT gittemoosknudsen synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT gittemoosknudsen synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT mikaelpalner synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT mikaelpalner synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease AT mikaelpalner synapticdensityandneuronalmetabolicfunctionmeasuredbypositronemissiontomographyintheunilateral6ohdaratmodelofparkinsonsdisease |
| _version_ |
1718424898503704576 |