[18F]fallypride-PET/CT Analysis of the Dopamine D2/D3 Receptor in the Hemiparkinsonian Rat Brain Following Intrastriatal Botulinum Neurotoxin A Injection

Molecules

Stefan Polei¹  Tobias Lindner¹  Jan Stenzel¹  Jens Kurth²  Alexander Hohn²  Bernd J. Krause²  Alexander Hawlitschka³  Andreas Wree³  Teresa Mann³ 

[1] Core Facility Multimodal Small Animal Imaging, Rostock University Medical Center, Schillingallee 69a, 18057 Rostock, Germany;Department of Nuclear Medicine, Rostock University Medical Centre, Gertrudenplatz 1, 18057 Rostock, Germany;Institute of Anatomy, Rostock University Medical Center, Gertrudenstrasse 9, 18057 Rostock, Germany;

关键词: D2/D3 receptors;    hemiparkinsonian rat model;    Botulinum neurotoxin A;    basal ganglia;    striatum;    Parkinson’s disease;    small animal imaging;    PET/CT;    [18F]fallypride;    MRI;   

DOI  :  10.3390/molecules23030587

来源: DOAJ

【 摘 要 】

Intrastriatal injection of botulinum neurotoxin A (BoNT-A) results in improved motor behavior of hemiparkinsonian (hemi-PD) rats, an animal model for Parkinson’s disease. The caudate–putamen (CPu), as the main input nucleus of the basal ganglia loop, is fundamentally involved in motor function and directly interacts with the dopaminergic system. To determine receptor-mediated explanations for the BoNT-A effect, we analyzed the dopamine D2/D3 receptor (D2/D3R) in the CPu of 6-hydroxydopamine (6-OHDA)-induced hemi-PD rats by [18F]fallypride-PET/CT scans one, three, and six months post-BoNT-A or -sham-BoNT-A injection. Male Wistar rats were assigned to three different groups: controls, sham-injected hemi-PD rats, and BoNT-A-injected hemi-PD rats. Disease-specific motor impairment was verified by apomorphine and amphetamine rotation testing. Animal-specific magnetic resonance imaging was performed for co-registration and anatomical reference. PET quantification was achieved using PMOD software with the simplified reference tissue model 2. Hemi-PD rats exhibited a constant increase of 23% in D2/D3R availability in the CPu, which was almost normalized by intrastriatal application of BoNT-A. Importantly, the BoNT-A effect on striatal D2/D3R significantly correlated with behavioral results in the apomorphine rotation test. Our results suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing interhemispheric changes of striatal D2/D3R.

【 授权许可】

Unknown