Parkinson's Disease Models
Creative Animodel offers an extensive portfolio of both in vitro and in vivo services in pharmacology and toxicology. Our rich-experienced scientists and state-of-art technique platforms assist the clients throughout every stage of the drug discovery process. We fully understand advantages and limitations of each animal model for investigating Parkinson’s disease, and will work side-by-side with you to decide the most appropriate model for your specific experimental hypotheses.
Overview of Parkinson's Disease
Although there have been several significant findings about the PD disease process, much of this process still remains unknown. A range of animal models has been used to study the pathogenic mechanisms and evaluate potential therapies of Parkinson’s disease. The current models tend to fall into two main categories.
• The first set of models focuses on toxin-induced lesions in which centrally or peripherally administered toxins more or less selectively destroy the dopaminergic nigrostriatal projection and produce clear motor deficits. For example muscarinic agonist’s tremorine and oxotremorine-induce tremor, ataxia, spasticity, salivation, lacrimation, and hypothermia parkinsonism-like signs.
• The second set of models includes animals with mutations either in genes known to be involved in the genetic form of PD or in the dopaminergic system. These genetic models often replicate particular aspects of the neuropathogenesis of the human disease (e.g., increased α-synuclein or reduced dopamine production), but with less prominent cell loss or motor symptoms than the toxin-induced models.
Figure 1. Loss of dopamine in PD.
Parkinson's Disease Models and Tests at Creative Animodel
• Unilateral or systemical parkinsonism
Animal models are established based on administration of toxins, either locally (6-hydroxydopamine, 6-OHDA; 1-methyl-4-phenyl-1,2,3,6-tetra- hydropyridine, MPTP) or systemically (reserpine, MPTP, rotenone, proteosomal inhibitors).
Reserpine induces depletion of central catecholamine stores. The sedative effect can be observed in mice shortly after injection, followed by signs of eyelid ptosis, hypokinesia, rigidity, catatonia, and immobility. These phenomena can be antagonized by dopamine agonists. We inject the mice intraperitoneally with reserpine and tested 24 h later. All the locomotor activity horizontal movements are recorded by our experienced observers.
N-MPTP (N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) has been shown to cause symptoms of PD in exposed individuals. When administered to primates this compound causes a partial destruction of basal ganglia and a syndrome that resembles PD. The pathological and biochemical changes produced by N-MPTP are similar to the well-established changes in patients with Parkinsonism.
• Human A53T alpha-synuclein transgenic mouse model
The transgenic mouse expresses the mutant human A53T alpha-synuclein under the direction of the mouse prion protein promoter. Neuronal loss and Lewy Bodies in the substantia nigra and locus ceruleus are associated with the A53T alpha-synuclein mutation.
• Oxotremorine-induced tremor model
PD is mainly distinguished from other diseases based on the key feature that is tremors. Oxotremorine-induced oxidative stress is implicated as a common pathway in the development of Parkinson’s symptoms like tremor, salivation and temperature variation. Hence, we use oxotremorine-induced tremor model to evaluate anti-Parkinsonian drugs. The oxotremorine antagonism has been proven to be a reliable method for testing central anticholinergic activity.
Model Characteristics and Pharmacology Evaluation
• Behavior assessment: olfactory, motor, somatosensory, cognition and gait analysis.
• Imaging analysis: MRI, PET, and quantitative autoradiography.
• Biochemical and routine parameters
• Quantitative analysis of proteins
• Various animal model selections: mice, rats, and non-human primates.
• Up-to-date facility and medical equipment, such as PET scan and MRI.
• Well-trained surgical and medical imaging teams.
• Talented and inspiration scientists in neurodegeneration diseases models.
Creative Animodel is dedicated to creating the most suitable animal models of Parkinson’s disease to advance the development for potential therapeutics into clinical studies. We will be with you on every step for obtaining meaningful and suggesting data from animal model studies for Parkinson’s disease. Please feel free to contact us for more information.
1. Ravi, S.K. Neuroprotective effects of Cassia tora against paraquat-induced neurodegeneration: relevance for Parkinson’s disease. Natural Product Research. 2017, doi: 10.1080/14786419.2017.1353504.