Elise Levigoureux1,2, Caroline Bouillot3, Thierry Baron4, Luc Zimmer1,2,3, Sophie Lancelot1,2,3. 1. Lyon Neuroscience Research Center, CNRS UMR5292, INSERM U1028, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France. 2. Hospices Civils de Lyon, Lyon, France. 3. CERMEP-Imaging Platform, Lyon, France. 4. ANSES - French Agency for Food, Environmental and Occupational Health & Safety, Lyon, France.
Abstract
AIMS: Alpha-synuclein (α-syn) aggregation is a neuropathological hallmark of neurodegenerative synucleinopathies. This in vivo study explored glucose metabolism and dopaminergic and serotoninergic neurotransmission in KO α-syn, wild-type mice and an accelerated murine model of synucleinopathy (M83). METHODS: MicroPET acquisitions were performed in all animals aged 5-6 months using five radiotracers exploring brain glucose metabolism ([18 F]FDG), dopamine neurotransmission ([11 C]raclopride, [11 C]PE2I) and serotonin neurotransmission ([18 F]MPPF, [11 C]DASB). For all radiotracers, except [18 F]FDG, PET data were analyzed with a MRI-based VOI method and a voxel-based analysis. RESULTS: MicroPET data showed a decrease in [11 C]raclopride uptake in the caudate putamen of KO α-syn mice, in comparison with M83 and WT mice, reflecting a lower concentration of D2 receptors. The increase in [18 F]MPPF uptake in M83 vs WT and KO mice indicates overexpression of 5-HT1A receptors. The lack of change in dopamine and serotonin transporters in all groups suggests unchanged neuronal density. CONCLUSIONS: This PET study highlights an effect of α-syn modulation on the expression of the D2 receptor, whereas aggregated α-syn leads to overexpression of 5-HT1A receptor, as a pathophysiological signature.
AIMS: Alpha-synuclein (α-syn) aggregation is a neuropathological hallmark of neurodegenerative synucleinopathies. This in vivo study explored glucose metabolism and dopaminergic and serotoninergic neurotransmission in KO α-syn, wild-type mice and an accelerated murine model of synucleinopathy (M83). METHODS: MicroPET acquisitions were performed in all animals aged 5-6 months using five radiotracers exploring brain glucose metabolism ([18 F]FDG), dopamine neurotransmission ([11 C]raclopride, [11 C]PE2I) and serotonin neurotransmission ([18 F]MPPF, [11 C]DASB). For all radiotracers, except [18 F]FDG, PET data were analyzed with a MRI-based VOI method and a voxel-based analysis. RESULTS: MicroPET data showed a decrease in [11 C]raclopride uptake in the caudate putamen of KO α-syn mice, in comparison with M83 and WT mice, reflecting a lower concentration of D2 receptors. The increase in [18 F]MPPF uptake in M83 vs WT and KO mice indicates overexpression of 5-HT1A receptors. The lack of change in dopamine and serotonin transporters in all groups suggests unchanged neuronal density. CONCLUSIONS: This PET study highlights an effect of α-syn modulation on the expression of the D2 receptor, whereas aggregated α-syn leads to overexpression of 5-HT1A receptor, as a pathophysiological signature.
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