PET imaging in animal models of Parkinson's disease.

Abstract

Alpha-synucleinopathies, such as Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, are characterized by aberrant accumulation of alpha-synuclein and synaptic dysfunction leading to motor and cognitive deficits. Animal models of alpha-synucleinopathy have greatly facilitated the mechanistic understanding of the disease and the development of therapeutics. Various transgenic, alpha-synuclein fibril-injected, and toxin-injected animal models of Parkinson's disease and multiple system atrophy that recapitulate the disease pathology have been developed and widely used. Recent advances in positron emission tomography have allowed the noninvasive visualization of molecular alterations, underpinning behavioral dysfunctions in the brains of animal models and the longitudinal monitoring of treatment effects. Imaging studies in these disease animal models have employed multi-tracer PET designs to reveal dopaminergic deficits together with other molecular alterations. This review focuses on the development of new positron emission tomography tracers and studies of alpha-synuclein, synaptic vesicle glycoprotein 2A neurotransmitter receptor deficits such as dopaminergic receptor, dopaminergic transporter, serotonergic receptor, vesicular monoamine transporter 2, hypometabolism, neuroinflammation, mitochondrial dysfunction and leucine rich repeat kinase 2 in animal models of Parkinson's disease. The outstanding challenges and emerging applications are outlined, such as investigating the gut-brain-axis by using positron emission tomography in animal models, and provide a future outlook.