Axonal degeneration in Parkinson's disease – Basal ganglia circuitry and D2 receptor availability

Abstract

Basal ganglia (BG) circuitry plays a crucial role in the control of movement. Degeneration of its pathways and imbalance of dopaminergic signalling goes along with movement disorders such as Parkinson's disease. In this study, we explore the interaction of degeneration in two BG pathways (the nigro-striatal and dentato-pallidal pathway) with D2 receptor signalling to elucidate an association to motor impairment and medication response.Included in the study were 24 parkinsonian patients [male, 62 years (± 9.3 SD)] compared to 24 healthy controls [male, 63 years (± 10.2 SD)]; each participant passed through three phases of the study (i) acquisition of metadata/clinical testing, (ii) genotyping and (iii) anatomical/diffusion MRI.We report a decline in nigro-striatal (p .05).Interplay between basal ganglia connectivity and D2 receptor availability influence the clinical presentation and medication response of parkinsonian patients. Furthermore, while current models of basal-ganglia function emphasize that balanced activity in the direct and indirect pathways is required for normal movement, our data highlight a role of the cerebellum in compensating for physiological imbalances in this respect. Keywords: Parkinson's disease, BG circuitry, D2 receptor polymorphism, Motor output, Treatment response