Elevated Type 1 Metabotropic Glutamate Receptor Availability in a Mouse Model of Huntington's Disease: a Longitudinal PET Study.

ABSTRACT: Impairment of group I metabotropic glutamate receptors (mGluRs) results in altered glutamate signalling, which is associated with several neurological disorders including Huntington's 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: +?15.0%, +?17.9%, and +?17.6% at 6, 12, and 16 months, respectively; p?

SUBMITTER: Bertoglio D 

PROVIDER: S-EPMC7118044 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature