In vivo quantification of glial activation in minipigs overexpressing human α-synuclein

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Thea Pinholt LillethorupAnne M Landau

Abstract

Parkinson's disease is characterized by a progressive loss of substantia nigra (SN) dopaminergic neurons and the formation of Lewy bodies containing accumulated alpha-synuclein (α-syn). The pathology of Parkinson's disease is associated with neuroinflammatory microglial activation, which may contribute to the ongoing neurodegeneration. This study investigates the in vivo microglial and dopaminergic response to overexpression of α-syn. We used positron emission tomography (PET) and the 18 kDa translocator protein radioligand, [11 C](R)PK11195, to image brain microglial activation and (+)-α-[11 C]dihydrotetrabenazine ([11 C]DTBZ), to measure vesicular monoamine transporter 2 (VMAT2) availability in Göttingen minipigs following injection with recombinant adeno-associated virus (rAAV) vectors expressing either mutant A53T α-syn or green fluorescent protein (GFP) into the SN (4 rAAV-α-syn, 4 rAAV-GFP, 5 non-injected control minipigs). We performed motor symptom assessment and immunohistochemical examination of tyrosine hydroxylase (TH) and transgene expression. Expression of GFP and α-syn was observed at the SN injection site and in the striatum. We observed no motor symptoms or changes in striatal [11 C]DTBZ binding potential in vi...Continue Reading

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Citations

Oct 26, 2018·Scientific Reports·Thea P LillethorupAnne M Landau
Jun 10, 2020·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Majken Borup ThomsenAnne M Landau
May 10, 2021·Experimental Neurology·K H BindaA M Landau
Jul 11, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Nadja Van CampHervé Boutin

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