parkinson's disease models - preclinical services

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Preclinical efficacy testing in models of Parkinson's Disease

MD Biosciences performs efficacy studies for proof-of-concept as well as assays for early screening and profiling of drug candidates. If there is a model or assay that you don't see listed, please contact a representative to discuss a custom assay design.

 

MPTP-induced PD-like Disease

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropryidine) is an effective dopaminergic neurotoxin that selectively destroys dopamine neurons in the substantia nigra, resulting in a Parkinson's-like syndrome. This model is an acute histology based model mimicking a depletion of 50-60% in Tyrosine-hydroxilase (TH) immunoreactive cells at the level of the Substantia Nigra pars compacta (SNpc) without affecting the general motor activity of the mice. The effect is less pronounced in the nucleus accumbance, olfactory tubercle and ventral tegmental. Since in MPTP lesioned mice the biochemical and morphological effects are bilateral, the detection of motor deficit is based on spontaneous locomotion observation such as open field test or on accelerating rotarod test.

Actute MPTP model
A week following administration of MPTP, the brains are evaluated for the presence of TH immunoreactive cells at the level of the SNpc.

Chronic MPTP model
This model combines the depletion in the TH immunoreactive cells with a decrease in motor activity. The benefit of the chronic model is that we are able to monitor motor function in addition to the histological assessment of DAmergic (dopaminergic) neuron depletion.

 

6OHDA-induced PD-like Disease

The 6OHDA (6-hydroxydopamine) induced model is a unilateral lesion model of which the Nigro-Striatial pathway is damaged. Unilateral dopamine (DA) denervation induces a number of behavorial deficits similar to those observed in patients with PD. A variety of tests are used to evaluate spontaneous and drug induced behavorial changes.

 

Parkinson's Disease
Parkinon's Disease (PD) is a neurogenerative disorder characterized by reduction in striatial (DA) content caused by the loss of dopaminergenic neurons in the Substantia Nigra part compacta (SNpc) and their proportions to the striatum. Several neurotoxins induced PD-like neuropathology in animals, includeing the neurotoxins 6-hydroxydopamine (6OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). These models mimic the depletion in dopaminergic (DAmergic) cells.

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