Progressive changes of pre- and post-synaptic dopaminergic biomarkers in conscious MPTP-treated cynomolgus monkeys measured by positronemission tomography
Article first published online: 27 JUN 2007
Copyright © 2007 Wiley-Liss, Inc.
Volume 61, Issue 10, pages 809–819, October 2007
How to Cite
Nagai, Y., Obayashi, S., Ando, K., Inaji, M., Maeda, J., Okauchi, T., Ito, H. and Suhara, T. (2007), Progressive changes of pre- and post-synaptic dopaminergic biomarkers in conscious MPTP-treated cynomolgus monkeys measured by positronemission tomography. Synapse, 61: 809–819. doi: 10.1002/syn.20431
- Issue published online: 27 JUN 2007
- Article first published online: 27 JUN 2007
- Manuscript Accepted: 11 APR 2007
- Manuscript Received: 2 NOV 2006
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japanese Government
- Parkinson model;
- Macaca fascicularis;
Positron emission tomography (PET) is a useful technique for the consecutive investigation of the relationship between changes in neurotransmission biomarkers and behavioral signs in animal models of Parkinson's disease (PD). In this study, we aimed to investigate the threshold of dopamine (DA) neuron damage for the appearance of tremor by observing the longitudinal changes of pre- and post-synaptic DA biomarkers in awake monkeys using PET with multiple tracers. Three cynomolgus monkeys were treated with MPTP every 3–6 weeks until tremor was observed. Brain uptake of [11C]PE2I, [β-11C]DOPA, and [11C]raclopride for DA transporter (DAT), DOPA utilization, and DA D2 receptor were measured using PET as a single set in awake condition. Sets of PET scans were repeated in parallel with continuous behavioral estimation. The pre-synaptic biomarkers of DA neuron in the striatum decreased [11C]PE2I binding and [β-11C]DOPA uptake in an MPTP dose-dependent manner. Tremor was not observed until striatal [11C]PE2I binding was reduced to about 15% of the pretreatment level and [β-11C]DOPA uptake was reduced to about 34%. DA D2 receptor measured by [11C]raclopride was not significantly changed throughout the experiment. Our results revealed that it is possible to quantitatively define the threshold of the onset of behavioral PD signs by monitoring spontaneous motor activity, and in vivo PET with DAT marker can be a biomarker for early diagnosis at the presymptomatic stage of PD and for high-risk groups. Synapse 61:809–819, 2007. © 2007 Wiley-Liss, Inc.