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Increased P2X7 Receptor Binding Is Associated With Neuroinflammation in Acute but Not Chronic Rodent Models for Parkinson's Disease.
Front Neurosci 2019; 13:799FN

Abstract

The purinergic P2X7 receptor is a key mediator in (neuro)inflammation, a process that is associated with neurodegeneration and excitotoxicity in Parkinson's disease (PD). Recently, P2X7 imaging has become possible with [11C]JNJ-(54173)717. We investigated P2X7 availability, in comparison with availability of the translocator protein (TSPO), in two well-characterized rat models of PD using in vitro autoradiography at multiple time points throughout the disease progression. Rats received either a unilateral injection with 6-hydroxydopamine (6-OHDA) in the striatum, or with recombinant adeno-associated viral vector overexpressing human A53T alpha-synuclein (α-SYN) in the substantia nigra. Transverse cryosections were incubated with [11C]JNJ-717 for P2X7 or [18F]DPA-714 for TSPO. [11C]JNJ-717 binding ratios were transiently elevated in the striatum of 6-OHDA rats at day 14-28 post-injection, with peak P2X7 binding at day 14. This largely coincided with the time course of striatal [18F]DPA-714 binding which was elevated at day 7-21, with peak TSPO binding at day 7. Increased P2X7 availability co-localized with microglial, but not astrocyte or neuronal markers. In the chronic α-SYN model, no significant differences were found in P2X7 binding, although in vitro TSPO overexpression was reported previously. This first study showed an increased P2X7 availability in the acute PD model in a time window corresponding with elevated TSPO binding and motor behavior changes. In contrast, the dynamics of TSPO and P2X7 were divergent in the chronic α-SYN model where no P2X7 changes were detectable. Overall, extended P2X7 phenotyping is warranted prior to implementation of P2X7 imaging for monitoring of neuroinflammation.

Authors+Show Affiliations

Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, University Hospital Leuven, KU Leuven, Leuven, Belgium. Molecular Small Animal Imaging Center, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.Laboratory for Neurobiology and Gene therapy, Department of Neurosciences, KU Leuven, Leuven, Belgium. Leuven Viral Vector Core, KU Leuven, Leuven, Belgium.Laboratory of Neuronal Circuit Development and Regeneration, Department of Biology, KU Leuven, Leuven, Belgium.Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, University Hospital Leuven, KU Leuven, Leuven, Belgium. Molecular Small Animal Imaging Center, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.Laboratory for Neurobiology and Gene therapy, Department of Neurosciences, KU Leuven, Leuven, Belgium. Leuven Viral Vector Core, KU Leuven, Leuven, Belgium. Leuven Brain Institute, KU Leuven, Leuven, Belgium.Molecular Small Animal Imaging Center, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. Radiopharmaceutical Research, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, University Hospital Leuven, KU Leuven, Leuven, Belgium. Molecular Small Animal Imaging Center, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.Laboratory of Neuronal Circuit Development and Regeneration, Department of Biology, KU Leuven, Leuven, Belgium. Leuven Brain Institute, KU Leuven, Leuven, Belgium.Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, University Hospital Leuven, KU Leuven, Leuven, Belgium. Molecular Small Animal Imaging Center, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31417352

Citation

Crabbé, Melissa, et al. "Increased P2X7 Receptor Binding Is Associated With Neuroinflammation in Acute but Not Chronic Rodent Models for Parkinson's Disease." Frontiers in Neuroscience, vol. 13, 2019, p. 799.
Crabbé M, Van der Perren A, Bollaerts I, et al. Increased P2X7 Receptor Binding Is Associated With Neuroinflammation in Acute but Not Chronic Rodent Models for Parkinson's Disease. Front Neurosci. 2019;13:799.
Crabbé, M., Van der Perren, A., Bollaerts, I., Kounelis, S., Baekelandt, V., Bormans, G., ... Van Laere, K. (2019). Increased P2X7 Receptor Binding Is Associated With Neuroinflammation in Acute but Not Chronic Rodent Models for Parkinson's Disease. Frontiers in Neuroscience, 13, p. 799. doi:10.3389/fnins.2019.00799.
Crabbé M, et al. Increased P2X7 Receptor Binding Is Associated With Neuroinflammation in Acute but Not Chronic Rodent Models for Parkinson's Disease. Front Neurosci. 2019;13:799. PubMed PMID: 31417352.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased P2X7 Receptor Binding Is Associated With Neuroinflammation in Acute but Not Chronic Rodent Models for Parkinson's Disease. AU - Crabbé,Melissa, AU - Van der Perren,Anke, AU - Bollaerts,Ilse, AU - Kounelis,Savannah, AU - Baekelandt,Veerle, AU - Bormans,Guy, AU - Casteels,Cindy, AU - Moons,Lieve, AU - Van Laere,Koen, Y1 - 2019/07/31/ PY - 2019/04/05/received PY - 2019/07/17/accepted PY - 2019/8/17/entrez PY - 2019/8/17/pubmed PY - 2019/8/17/medline KW - 6-OHDA KW - P2X7 KW - Parkinson’s disease KW - translocator protein KW - α-synuclein SP - 799 EP - 799 JF - Frontiers in neuroscience JO - Front Neurosci VL - 13 N2 - The purinergic P2X7 receptor is a key mediator in (neuro)inflammation, a process that is associated with neurodegeneration and excitotoxicity in Parkinson's disease (PD). Recently, P2X7 imaging has become possible with [11C]JNJ-(54173)717. We investigated P2X7 availability, in comparison with availability of the translocator protein (TSPO), in two well-characterized rat models of PD using in vitro autoradiography at multiple time points throughout the disease progression. Rats received either a unilateral injection with 6-hydroxydopamine (6-OHDA) in the striatum, or with recombinant adeno-associated viral vector overexpressing human A53T alpha-synuclein (α-SYN) in the substantia nigra. Transverse cryosections were incubated with [11C]JNJ-717 for P2X7 or [18F]DPA-714 for TSPO. [11C]JNJ-717 binding ratios were transiently elevated in the striatum of 6-OHDA rats at day 14-28 post-injection, with peak P2X7 binding at day 14. This largely coincided with the time course of striatal [18F]DPA-714 binding which was elevated at day 7-21, with peak TSPO binding at day 7. Increased P2X7 availability co-localized with microglial, but not astrocyte or neuronal markers. In the chronic α-SYN model, no significant differences were found in P2X7 binding, although in vitro TSPO overexpression was reported previously. This first study showed an increased P2X7 availability in the acute PD model in a time window corresponding with elevated TSPO binding and motor behavior changes. In contrast, the dynamics of TSPO and P2X7 were divergent in the chronic α-SYN model where no P2X7 changes were detectable. Overall, extended P2X7 phenotyping is warranted prior to implementation of P2X7 imaging for monitoring of neuroinflammation. SN - 1662-4548 UR - https://www.unboundmedicine.com/medline/citation/31417352/Increased_P2X7_Receptor_Binding_Is_Associated_With_Neuroinflammation_in_Acute_but_Not_Chronic_Rodent_Models_for_Parkinson's_Disease L2 - https://dx.doi.org/10.3389/fnins.2019.00799 DB - PRIME DP - Unbound Medicine ER -