In vivo 18 F-DOPA PET imaging identifies a dopaminergic deficit in a rat model with a G51D α-synuclein mutation.

Autor: Morley V; Centre for Regenerative Medicine, Institute for Regeneration and Repair, School of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom., Dolt KS; Centre for Regenerative Medicine, Institute for Regeneration and Repair, School of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom., Alcaide-Corral CJ; University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom., Walton T; University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom., Lucatelli C; University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom., Mashimo T; Division of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan., Tavares AAS; University/BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, The University of Edinburgh, Edinburgh, United Kingdom., Kunath T; Centre for Regenerative Medicine, Institute for Regeneration and Repair, School of Biological Sciences, The University of Edinburgh, Edinburgh, United Kingdom.
Jazyk: angličtina
Zdroj: Frontiers in neuroscience [Front Neurosci] 2023 May 24; Vol. 17, pp. 1095761. Date of Electronic Publication: 2023 May 24 (Print Publication: 2023).
DOI: 10.3389/fnins.2023.1095761
Abstrakt: Parkinson's disease (PD) is a neurodegenerative condition with several major hallmarks, including loss of substantia nigra neurons, reduction in striatal dopaminergic function, and formation of α-synuclein-rich Lewy bodies. Mutations in SNCA , encoding for α-synuclein, are a known cause of familial PD, and the G51D mutation causes a particularly aggressive form of the condition. CRISPR/Cas9 technology was used to introduce the G51D mutation into the endogenous rat SNCA gene. SNCA G51D/+ and SNCA G51D/G51D rats were born in Mendelian ratios and did not exhibit any severe behavourial defects. L -3,4-dihydroxy-6- 18 F-fluorophenylalanine ( 18 F-DOPA) positron emission tomography (PET) imaging was used to investigate this novel rat model. Wild-type (WT), SNCA G51D/+ and SNCA G51D/G51D rats were characterized over the course of ageing (5, 11, and 16 months old) using 18 F-DOPA PET imaging and kinetic modelling. We measured the influx rate constant ( K i ) and effective distribution volume ratio ( EDVR ) of 18 F-DOPA in the striatum relative to the cerebellum in WT, SNCA G51D/+ and SNCA G51D/G51D rats. A significant reduction in EDVR was observed in SNCA G51D/G51D rats at 16 months of age indicative of increased dopamine turnover. Furthermore, we observed a significant asymmetry in EDVR between the left and right striatum in aged SNCA G51D/G51D rats. The increased and asymmetric dopamine turnover observed in the striatum of aged SNCA G51D/G51D rats reflects one aspect of prodromal PD, and suggests the presence of compensatory mechanisms. SNCA G51D rats represent a novel genetic model of PD, and kinetic modelling of 18 F-DOPA PET data has identified a highly relevant early disease phenotype.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Morley, Dolt, Alcaide-Corral, Walton, Lucatelli, Mashimo, Tavares and Kunath.)
Databáze: MEDLINE
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