Shed Light on Dopamine D2 Receptors and Dyskinesia
Our well-coordinated movements depend on the functional interaction between two neural pathways within the basal ganglia. These pathways originate from striatal neurons that express different types of dopamine receptors. Specifically, neurons giving rise to the so-called direct pathway express the D1 receptor type, whereas neurons forming the indirect pathway express the D2 receptor type. In Parkinson’s disease (PD), a severe dopamine depletion causes insufficient stimulation of both D1 and D2 receptors, disrupting the physiological interplay between direct and indirect pathway. Further imbalances in pathway activation are caused by L-DOPA, a dopamine precursor that provides the main treatment for PD. While L-DOPA is initially effective in improving parkinsonian motor symptoms, it induces different types of abnormal involuntary movements, termed L-DOPA-induced dyskinesia (LID), within a few years of treatment.
During the past years, the role of dopamine D1 receptor in LID has been largely addressed, pointing out how the overstimulation of this receptor and its pathway was “necessary and sufficient” to induce dyskinesia. However, the current model is inadequate to explain why dyskinesia still affects the majority of persons with Parkinson’s (PwP) undergoing pharmacological treatments targeting the dopamine D2/D3 receptors, rather than the D1. Parkinsonian dyskinesias are often represented as a complex pattern of movements; a mixture of choreatic gestures and abnormal dystonic postures. The heterogeneity by which these movements manifest from one person with Parkinson’s to another, makes us wonder whether dyskinesias can really relate to the activity of one single receptor. To our matter, how D1 and D2 receptors stimulation differently contributes to the genesis of dyskinetic movements in PD is an important scientific and clinical question that clearly deserves more investigation.
At the 5th World Parkinson Congress meeting in Kyoto, I had the opportunity to share my research with a poster entitled “Role of indirect pathway D2 receptors in L-DOPA-induced dyskinesia”. In this study we focus on understanding the specific contribution of dopamine D2 receptors to different types of dyskinetic behaviors, by using a combination of selective knock-out strategies and a mouse model of Parkinson´s disease.
WPC 2019 in Kyoto was my first World Parkinson Congress. A bit overwhelming at first, the congress revealed its unique format with nearly 3,000 delegates, representing the full Parkinson’s community. This mix allowed clinicians, researchers, care partners and people with Parkinson’s to not only meet each other but learn and share their experiences. As a basic scientist it was a new experience for me! Since I left the congress, I have been able to finalize part of the data presented in the poster and together with my colleagues we aim to publish the study by the end of 2020. I hope our understanding of this subject will contribute to better determine the choice of more personalized antidyskinetic treatments in the future and look forward to sharing new research at the WPC 2022 in Barcelona.
Laura Andreoli is a PhD student at the Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science at Lund University, Sweden.
This research was first shared as an abstract at the WPC 2019 in Kyoto. WPC is pleased to support abstract authors by sharing their ongoing work. Digital versions of WPC abstract books can be downloaded from the past three Congresses HERE.
Ideas and opinions expressed in this post reflect that of the author(s) solely. They do not necessarily reflect the opinions of the World Parkinson Coalition®