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

被引：5

作者：

Bertoglio, Daniele ^{[1
]}

Verhaeghe, Jeroen ^{[1
]}

Korat, Spela ^{[1
,2
]}

Miranda, Alan ^{[1
]}

Cybulska, Klaudia ^{[1
,2
]}

Wyffels, Leonie ^{[1
,2
]}

Stroobants, Sigrid ^{[1
,2
]}

Mrzljak, Ladislav ^{[3
]}

Dominguez, Celia ^{[3
]}

Skinbjerg, Mette ^{[3
]}

Liu, Longbin ^{[3
]}

Munoz-Sanjuan, Ignacio ^{[3
]}

Staelens, Steven ^{[1
]}

机构：

[1] Univ Antwerp, Mol Imaging Ctr Antwerp, Antwerp, Belgium

[2] Antwerp Univ Hosp, Dept Nucl Med, Edegem, Belgium

[3] CHDI Management CHDI Fdn, Los Angeles, CA USA

来源：

MOLECULAR NEUROBIOLOGY | 2020年 / 57卷 / 04期

关键词：

C-11]ITDM; Glutamate; mGluR1; Brain imaging; Receptor; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; REFERENCE TISSUE MODEL; TRAFFICKING; BINDING;

D O I：

10.1007/s12035-019-01866-5

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 [C-11]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 (V-T (IDIF)) and voxel-wise parametric V-T (IDIF) maps were performed to assess differences between genotypes. Post-mortem evaluation at 16 months was done to support in vivo findings. [C-11]ITDM V-T (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 < 0.001). In addition, an age-related decline in [C-11]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 [C-11]ITDM PET imaging demonstrated higher [C-11]ITDM binding in extra-striatal brain regions during the course of disease in the Q175DN mouse model.

引用

页码：2038 / 2047

页数：10

共 46 条

[1] Modulation of mTOR and CREB pathways following mGluR5 blockade contribute to improved Huntington's pathology in zQ175 mice [J].