Bertoglio, Daniele

Cybulska, Klaudia

Dominguez, Celia

Korat, \u160pela

Liu, Longbin

Miranda Menchaca, Alan

Mrzljak, Ladislav

Munoz-Sanjuan, Ignacio

Skinbjerg, Mette

Staelens, Steven

Stroobants, Sigrid

Verhaeghe, Jeroen

Wyffels, Leonie

Abstract: Impairment of group I metabotropic glutamate receptors (mGluRs) results in altered glutamate signalling, which is associated with several neurological disorders including Huntington\u2019s Disease (HD), an autosomal neurodegenerative disease. In this study, we assessed in vivo pathological changes in mGluR1 availability in the Q175DN mouse model of HD using longitudinal positron emission tomography (PET) imaging with the radioligand [11C]ITDM. Ninety-minute dynamic PET imaging scans were performed in 22 heterozygous (HET) Q175DN mice and 22 wild-type (WT) littermates longitudinally at 6, 12, and 16 months of age. Analyses of regional volume of distribution with an image-derived input function (VT (IDIF)) and voxel-wise parametric VT (IDIF) maps were performed to assess differences between genotypes. Post-mortem evaluation at 16 months was done to support in vivo findings. [11C]ITDM VT (IDIF) quantification revealed higher mGluR1 availability in the brain of HET mice compared to WT littermates (e.g. cerebellum: +\u200915.0%, +\u200917.9%, and +\u200917.6% at 6, 12, and 16 months, respectively; p\u2009<\u20090.001). In addition, an age-related decline in [11C]ITDM binding independent of genotype was observed between 6 and 12 months. Voxel-wise analysis of parametric maps and post-mortem quantifications confirmed the elevated mGluR1 availability in HET mice compared to WT littermates. In conclusion, in vivo measurement of mGluR1 availability using longitudinal [11C]ITDM PET imaging demonstrated higher [11C]ITDM binding in extra-striatal brain regions during the course of disease in the Q175DN mouse model

Institutional Repository Universiteit Antwerpen

Elevated type 1 metabotropic glutamate receptor availability in a mouse model of Huntington\u2019s disease : a longitudinal PET study

Elevated type 1 metabotropic glutamate receptor availability in a mouse model of Huntington\u2019s disease : a longitudinal PET study

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Institutional Repository Universiteit Antwerpen