Complex Pathology
Parkinson’s Disease (PD) is typically an adult-onset progressive neurodegenerative movement disorder that affects millions of people worldwide. Pathologically, PD is characterized by the profound and specific loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) of the midbrain. The cardinal symptoms of PD include bradykinesia, resting tremor, rigidity, and postural instability. To date, research into the etiology of PD has revealed that most cases are sporadic, though some thirteen genetic loci have been identified to be disease-related. Examination of the biochemical properties of these mutant proteins and the pathways in which they are involved has led to the uncovering of three basic pathogenetic pathways common to both heritable and idiopathic forms of PD: abnormal protein control, mitochondrial dysfunction, and altered kinase activity.
Progress towards the identification of disease-related genes has thus led to the expansion of animal models of PD from the classic 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA)-induced neurotoxin models to genetic models of the disease. Due to its complex pathology, however, there is no animal disease model that replicates all aspects of human PD. With the evolution of such models, converging lines of evidence from toxin-induced and genetic models have continued to further our understanding of the pathological processes underlying PD and lend themselves as useful systems for the examination of therapeutic interventions.
Parkinson's Disease Models Offered
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PD Neurodegeneration In Vitro Screening Assay
A hallmark of degeneration is the blebbing of neurites, which is when neurites begin disassembly and degeneration. The neurodegeneration index (NI) compares the relative area of neurites and the number of neurites.
The PD in vitro screening assay utilizes primary neurons from immature mice or rats. Following the conditioning phase with a-synuclein, cultures are treated with compounds and evaluated for their neurodegeneration index.
The assays are ideal for screening compounds prior to efficacy in in vivo studies.
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6OHDA In Vivo Model
Our 6-hydroxydopamine (6OHDA) model is a unilateral lesion model in which the Nigro-Striatal pathway is damaged. Since systemically administered 6OHDA fails to cross the blood-brain barrier, we instead stereotaxically inject toxin directly into the brain region of interest, typically the substantia nigra (SN), ventral tegmental area (VTA) or striatum.
Assessments:
- Apomorphine-induced Rotations
- Paw Placement (scroll down to see test results)
- Histology/IHC
Example Data
Paw placement test was performed in rats at various time points throughout the study. Vehicle treated animals were compared to test therapy. -
Acute MPTP In Vivo Model
A standard animal model of PD is created by the systemic administration of MPTP, a highly lipophilic compound that readily crosses the blood-brain barrier. This mouse model is the most commonly used PD animal model, and is similar to the 6OHDA model in that the MPTP model shows selective degeneration of dopaminergic neurons. An additional benefit of this mouse model is that MPTP is known to cause a PD-like disease in humans by a similar mechanism of action. Unlike 6OHDA, MPTP itself is not an active neurotoxin. Rather, following systemic injection, it is taken up by glial cells, is converted to 1-methyl-4-phenyl-2,3-dihydropyridium (MPDP) by monoamine oxidase B (MAO B) and is rapidly oxidized to the active form 1-methyl-4-phenylpyridinium (MPP+). Upon release into the extracellular space, MPP+ is preferentially taken up by Dopaminergic neurons through DAT and most severely affects the SN. Similarly to 6-OHDA, MPP+ kills neurons by inhibiting complex I of the mitochondrial respiratory chain. As a result of these neurotoxic effects, MPTP-injected animals also display motor abnormalities.
Assessments:
- TH-IR immunoreactive analysis
Total count of Th-IR immunoreactive cells in naive and MPTP-induced animals.
Scientific Data
HC staining with Tyrosine Hydroxylase (TH) antibody.
Figure A. Subgross image of Substantia Nigra sections showing reduction in number of TH-positive cells in the right hemisphere vs. the left intact hemisphere. Figure B. High magnification of TH-positive dopaminergic neurons. Figure C. Subgross image of TH-positive nerve fibers in section of striatum of the Left intact hemisphere contrasted to the lack of TH staining in the right hemisphere injected with 6-OHDA.

Review the full dataset for models of PD.
PD Models Datasheet
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