PET imaging of the influence of physiological and pathological α-synuclein on dopaminergic and serotonergic neurotransmission in mouse models.
CNS Neurosci Ther
; 25(1): 57-68, 2019 01.
Article
en En
| MEDLINE
| ID: mdl-29781098
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Dopamina
/
Serotonina
/
Tomografía de Emisión de Positrones
/
Alfa-Sinucleína
Límite:
Animals
Idioma:
En
Revista:
CNS Neurosci Ther
Asunto de la revista:
NEUROLOGIA
/
TERAPEUTICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Francia