Magnetic resonance imaging characterization of an α‐synuclein model of Parkinson's disease

Abstract

AbstractParkinson's disease (PD) is primarily characterized by three histological hallmarks: dopaminergic neuronal degeneration, α‐synuclein accumulation and iron deposition. Over the last years, neuroimaging, particularly magnetic resonance imaging (MRI) has provided invaluable insights into the mechanisms underlying the disease. However, no imaging method has yet been able to translate α‐synuclein protein accumulation and spreading. Amongst the animal models mimicking the disease, the α‐synuclein rat, generated through the injection of human α‐synuclein, has been characterized in terms of behavioural and histological aspects but not thoroughly explored in MRI. The aim of this study is, therefore, to identify the radiological signature from several MRI sequences, while controlling for histological and behavioural characteristics. Rats were assessed for motor and cognitive functions over a 4‐month period. During this time, three MRI sessions, including both morphological and functional sequences, were conducted. Histological studies evaluated the three main hallmarks of PD. The progressive dopaminergic neurodegeneration and the spread of human α‐synuclein corresponded to the level of sensorimotor, attentional and learning deficits observed in this PD model. MRI analyses showed progressive structural abnormalities in the midbrain, diencephalon and several cortical structures, as well as a pattern of hyperconnectivity in the basal ganglia and cortical networks. The regions affected in imaging demonstrated the highest load of human α‐synuclein. This model's structural and functional MRI changes could serve as indirect indicators of α‐synuclein accumulation and its association with impaired non‐motor functions.