Abstract
Transgenic mice line M83 that express the A53T mutant α–synuclein protein at six times the level of endogenous mice α–synuclein are a model of α-synucleinopathy found in Parkinson’s disease (PD). This Hualpha-Syn (A53T) PD model is useful in assessing non-motor deficits at earlier stages of onset of PD. We report findings on metabolic changes using [18F]FDG PET/CT in the Hualpha-Syn (A53T) PD mouse model in comparison to non-carrier mice. Whole-body PET/CT imaging of male and female mice were carried out 2 h after [18F]FDG ip administration under 3% isoflurane anesthesia. Brain images were analyzed with PET images coregistered to a mouse brain MRI template. Hualpha-Syn (A53T) mice had significantly lower [18F]FDG uptake in several brain regions compared to the no-carrier mice. Significant hind limb muscle and lower spinal cord [18F]FDG hypometabolism at 9 months of age in A53T PD mice was also indicative of neurodegenerative disease, with a progressive motoric dysfunction leading to death. Significant decrease (up to 30%) in [18F]FDG uptake were observed in 9-month old male and female Hualpha-Syn (A53) mice. This is consistent with the cortical hypometabolism in PD patients. Hualpha-Syn (A53) mice may thus be a suitable model for studies related to PD α-synucleinopathy for the discovery of new biomarkers.
Highlights
Parkinson’s disease (PD) is a neurodegenerative disease which manifests in motor and non-motor ailments leading to cognitive impairment
Rodent models of motor deficits of PD, either by 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in mice or 6-hydroxy-DOPA in rats, causing loss of dopaminergic neurons in the striatum have been used in PET studies
We previously reported use of [18F]fallypride in an MPTP-treated mouse model to investigate effects of exercise (Vuckovic et al, 2010)
Summary
Parkinson’s disease (PD) is a neurodegenerative disease which manifests in motor and non-motor ailments leading to cognitive impairment. Aggregation of misfolded α-synuclein in intracellular inclusions, Lewy bodies (LB), are some of the hallmarks of human PD (Martí et al, 2003). Neuronal abnormalities displayed by affected mice include pathological accumulations of α-synuclein and ubiquitin. In the A35T α-Syn mutant mice, it was discovered that they attain intraneuronal inclusions, mitochondrial degeneration, and cell death in the neocortex, brainstem, and spinal cord. They formed inclusions similar to LB in neurons, and had profound deficits in their motor neurons, which could explain the paralysis in A53T line G2-3 mice (Martin et al, 2006).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
