Characterization of long-term motor deficits in the 6-OHDA model of Parkinson's disease in the common marmoset

Abstract

Research aimed at developing new therapies for Parkinson's disease (PD) critically depend on valid animal models of the disease that allows for repeated testing of motor disabilities over extended time periods. We here present an extensive characterization of a wide range of motor symptoms in the 6-OHDA marmoset model of PD when tested over several months. The severity of motor deficits was quantified in two ways: (i) through manual scoring protocols appropriately adapted to include species specific motor behavior and (ii) using automated quantitative motion tracking based on image processing of the digital video recordings. We show that the automated methods allow for rapid and reliable characterization of motor dysfunctions, thus complementing the manual scoring procedures, and that robust motor symptoms lasting for several months could be induced when using a two-stage neurotoxic lesioning procedure involving one hemisphere at a time. This non-human primate model of PD should therefore be well suited for long-term evaluation of novel therapies for treatment of PD.

Systems-level neurophysiological state characteristics for drug evaluation in an animal model of levodopa-induced dyskinesia

“…If more detailed behavioral assessments had been carried out with quantitative assessment scales that were adapted to include a wider range of motor symptoms, it is probable that the behavioral state descriptions would be better correlated to the neurophysiological activity states recorded in these motor circuits. Notably, however, such behavioral assessments are technically very challenging to carry out and will likely require more advanced automated procedures (e.g., Palmér et al 2012;Santana et al 2015). In addition, it is well-known that PD also includes nonmotor symptoms, and in several other disorders few overt signs, if any, may be associated with a specific pathological condition.…”

Non-human primates as a model for aging

“…The small body size of marmosets is particularly attractive for early stage pharmaceutical testing where smaller amounts of the substance would need to be produced than if using a larger bodied model. Marmosets have been particularly useful as a neurotoxin induced model of Parkinson’s disease [122] and more recently genetic models of Parkinson’s disease have been developed [123].…”

Modeling Parkinson's disease in the common marmoset (Callithrix jacchus): overview of models, methods, and animal care

“…Currently available genetic models do not completely induce appreciable neurodegeneration and PD phenotypes [ 35 ], whereas the neurotoxic models are used to damage the nigrostriatal pathway [ 10 ]. The marmoset model is a recognized model of PD using neurotoxins that induce the selective degeneration of nigrostriatal neurons [ 22 36 37 ]. The most commonly used toxins are 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA), which reproduce the pathological and behavioral changes of the human disease in rodents or NHPs.…”

“…In order to cure Parkinsonian symptoms, highly reproducible animal models of PD should be developed to address all PD-related questions including pathological changes in the brain. First, the occurrence of typical PD symptoms can be recorded using a clinical rating scale (apathy, immobility, muscle rigidity, tremors and inadequate grooming) and for the purpose of scoring abnormal involuntary movements (facial behaviors, full body behaviors, and general severity of involuntary movements and incapacitation due to these movements) ( Table 3 ) [ 36 58 72 73 ]. These clinical measurements can be performed in a double-blind manner by watching post hoc video-recordings of the animals accompanied by recording spontaneous locomotor activity in the lesioned animals [ 74 ].…”