Objective and quantitative evaluation of motor function in a monkey model of Parkinson's disease

Abstract

Monkeys treated with 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) are currently the best animal model for Parkinson's disease (PD) and have been widely used for physiological and pharmacological investigations. However, objective and quantitative assessments have not been established for grading their motor behaviors. In order to develop a method for an unbiased evaluation, we performed a video-based assessment, used qualitative rating scales, and carried out an in vivo investigation of dopamine (DA) transporter binding in systemically MPTP-treated monkeys. The video-based analysis of spontaneous movement clearly demonstrated a significant correlation with the qualitative rating score. The assessment of DA transporter (DAT) function by [(11)C]-CFT-PET showed that, when compared with normal animals, the MPTP-treated animals exhibited decreased CFT binding in the bilateral striatum, particularly in the dorsal part in the putamen and caudate. Among the MPTP-treated monkeys, an unbiased PET analysis revealed a significant correlation between CFT binding in the midbrain and qualitative rating scores or the amount of spontaneous movements. These results indicate that a video-based analysis can be a reliable tool for an objective and quantitative evaluation of motor dysfunction of MPTP-treated monkeys, and furthermore, that DAT function in the midbrain may also be important for the evaluation.

Autologous mesenchymal stem cell–derived dopaminergic neurons function in parkinsonian macaques

“…We performed 11 C-CFT PET scanning to evaluate DAT expression in cynomolgus brains, as described previously (26,62). The tracer 11 C-CFT was prepared by a conventional method using 11 C-methyl-triflate (63) and a precursor, nor[methyl-11 C]2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane.…”

“…For 11 C-CFT PET images, BPND images were preprocessed for voxel-based statistics using a previously described method (62). Briefly, the PET images were co-registered with MRI images (obtained at the time closest to the PET scan) using a rigid body transformation and transformed to the standard brain space of cynomolgus macaque (31).…”

Therapeutic Application of Stem Cell Technology toward the Treatment of Parkinson’s Disease

“…In general, dA neurotoxins, such as rotenone, 6-hydroxydopamine (6-OHdA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), are used to create parkinsonian animal models using rodents and non-human primates. 19) In particular, since the symptoms and brain anatomy of monkey models are similar to those of humans, and highresolution neuroimaging techniques are available to evaluate the function of dA neurons using positron emission tomography and magnetic resonance imaging, the same as they are for human patients, 20) the knowledge from monkey trials strongly contributes to the transition to human clinical trials.…”

A new quantitative rating scale for dyskinesia in nonhuman primates

“…Hence, a quantitative scale is needed to provide a standardized method for measuring dyskinesia. The number of methods for evaluating dyskinesia quantitatively in NHPs is limited and those that are currently available focus on the time spent in hyperactivity, overall locomotion, beam brakes etc., which actually lack of specificity for involuntary choreodystonic movements (Pearce et al ., 1995; Chassain et al ., 2001; Kuoppamaki et al ., 2007; Johnston et al ., 2010a; Saiki et al ., 2010). Thus, there remains a need for a scale that directly and quantifiably measures truly dyskinetic movements, and it is important that such a scale be simple yet comprehensive, in order to increase the sensitivity for detecting small variations in dyskinesias.…”