Decreased pallidal vesicular monoamine transporter type 2 availability in Parkinson's disease: The contribution of the nigropallidal pathway

• Published in: Neurobiology of disease 2019-04, Vol.124, p.176-182
• Main Authors: Cho, Sang Soo, Christopher, Leigh, Koshimori, Yuko, Li, Crystal, Lang, Anthony E., Houle, Sylvain, Strafella, Antonio P.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Basal Ganglia - diagnostic imaging; Basal Ganglia - metabolism; Dopamine; Dopaminergic Neurons - metabolism; Female; Globus pallidus; Globus Pallidus - diagnostic imaging; Globus Pallidus - metabolism; Humans; Male; Middle Aged; Neural Pathways - diagnostic imaging; Neural Pathways - metabolism; Parkinson Disease - diagnostic imaging; Parkinson Disease - metabolism; Parkinson's disease; Positron emission tomography; Substantia Nigra - diagnostic imaging; Substantia Nigra - metabolism; Vesicular Monoamine Transport Proteins - metabolism; Vesicular monoamine transporter type 2
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2018.11.022

To date, the contribution of the nigropallidal pathway degeneration to Parkinson's disease (PD) motor symptoms has received little attention and is generally poorly understood in spite of solid evidence that the globus pallidus (GP) receives a dense neuronal projection from the substantia nigra. To explore the dopaminergic (DA) changes of the GP in PD, we measured the availability of vesicular monoamine transporter 2 (VMAT2) using [11C]DTBZ and positron emission tomography in 30 PD patients and 12 controls. PD patients were classified in two groups based on severity of disease. VMAT2 reduction was found to be significant in the external GP (GPe) regardless of the disease stage, while the internal GP (GPi) showed reduction only in more severe patients. Pallidal VMAT2 binding correlated with dopaminergic changes in the striatum, with the GPe showing a stronger association than GPi. Our findings showed DA terminals in the GPe and GPi may be differentially vulnerable in different stages of the disease, possibly playing a distinctive role in the development of motor complications with GPi DA deficiency contributing more to later-stage symptoms. •The globus pallidus is a major output structure of the basal ganglia, involved in the regulation of voluntary movement.•The relationship between degeneration of the nigro-pallidal pathway and PD motor symptoms is poorly understood.•Results confirmed the degeneration not only in the nigrostriatal but also in the nigro-pallidal dopaminergic pathway.•Globus pallidus substructures have different vulnerability in PD, with the internal globus pallidus contributing more to later-stage.