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A non-human primate model for stable chronic Parkinson’s disease induced by MPTP administration based on individual behavioral quantification

2019.01.01.

Jincheol Seo et al., Journal of Neuroscience Methods, 2019

Summary

Parkinson’s disease (PD) is a neurodegenerative disease that affects about 3% of the population over 65 years of age. PD is characterized by a selective loss of dopaminergic neurons accompanied by movement disorders, including rigidity, bradykinesia, akinesia, tremors, and postural instability.

The authors aimed to develop a MPTP-induced chronic NHP model with stable symptoms by adjusting MPTP treatment based on individual behavioral quantification using a video-based analysis system. To validate this strategy, they assessed a parkinsonian behavior score, an immunohistochemistry Western blot, and PET imaging of dopamine transporter (DAT) with [18F] N-(3-fluoropropyl)-2ß-carboxymethoxy-3β-(4-iodophenyl) nortropane (18F-FP-CIT).

The authors stated that the novel strategy of MPTP administration based on global activity evaluations using a video-based analysis system provides an important conceptual advance of this method for the development of chronic NHP PD models.

Results from nanoScan® PET/CT

Mediso’s nanoScan PET/CT with 16cm bore size, 12 cm transaxial and 10 cm axial Field of View (FOV) were suitable to execute PET/CT scans in cynomolgus monkeys (Macaca fascicularis). Furthermore high spatial and temporal resolution of PET allowed to determine the dopamine transporter biding potential (BP) in different striatal sub-regions.

Following a CT scan for attenuation correction, 185 MBq 18 F-FP-CIT in 1.5 ml saline was injected intravenously via the saphenous vein. To monitor presynaptic dopamine transporter activity in vivo, serial 18F-FP-CIT PET imaging was performed after MPTP administration.

  • The biding potential analysis revealed that the 18F-FP-CIT BP were significantly reduced in all sub-regions of the striatum at 8, 16, 24, 32,40 and 48 weeks following the first MPTP administration (Fig. 4A and 4B).
  • Monkeys with fewer striatal DAT tended to have lower global activity (GA), indicating that a decrease in GA reflects damage in dopaminergic neurons.
  • The severity of Parkinsonian symptoms and the loss rates of DAT in each striatal sub-region did not correlate with the total dose of MPTP, indicating that a fixed MPTP dose is not a good strategy for development of chronic NHP PD models

Fig. 4. (A) Representative 18F-FP-CIT PET images fused with individual MRI. (B) Histogram representing 18F-FP-CIT binding potential (BP) in the MPTP-injection group. (#P < 0.05, *P<0.01 vs. baseline). (C) Histogram representing time activity curve. The radiotracer uptake in each region of interest was estimated as the standardized uptake value (SUV), which was calculated as decay-corrected activity per milliliter of tissue volume per injected radiotracer activity per body mass ([kBq/mL]/[kBq/g]). Ant, anterior; binding potential, BP; Ext, external; pallidum, globus pallidus; Int, internal; Post, posterior.

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