Parkinson's Disease In Vitro Disease Models and PD Screening Assays

Parkinson’s disease (PD) is caused by specific loss of dopaminergic neurons in the substantia nigra/midbrain and resulting lack of neuronal signals into the striatum which leads to motor and cognitive dysfunctions. Parkinson’s disease etiology is only partially understood. Disease models cover a wide range of approaches by using Parkinsonism provoking agents as MPP+, Rhotenon or 6-OHDA or modeling this neurodegenerative disease with suspected disease relevant proteins as alpha-synuclein filaments. The third kind of approaches uses genetically modified cell lines with Parkinson’s disease causing mutations as A53T, LRRK2 or PARK mutation to call only two. Patient-derived human cell lines established via iPSC reprogramming and differentiating of these toward dopaminergic cell cultures with a ventral midbrain type with Parkinson mutations have a great promise for better and more predictive disease models. For this NeuroProof has developed different dopaminergic cell culture protocols on microelectrode arrays, for more information, see our page on neural stem stells.

Parkinson’s Disease MPP+Assay with dopaminergic neuronal cell cultures

Neuronal in vitro disease models containing dopaminergic neurons allow the testing of PD drug candidates. One of these established in vitro models is based on MPP+, 1-methyl-4-phenylpyridinium, which is the metabolite of MPTP, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridin, a neurotoxin which causes symptoms of Parkinson’s disease. MPP+ induces oxidative stress and neurotoxicity specifically affecting dopaminergic neurons. The NeuroProof platform is able to quantify functional effects before these neurotoxic, i.e. cytotoxic events are induced, which of course affect the neuronal network activity dramatically induced by loss of neurons.

We investigate the functional effects induced by MPP+ at a concentration which affects neuronal activity, neurite and synapse morphology but not yet kills neurons. Thus, we focus on the early pathophysiological effects of PD and show that a pre-treatment with endogenous trophic factors such as GDNF or BDNF is able to prevent the functional and morphological effects.

We offer this screening of neuroprotective compounds on both primary midbrain neurons and on human iPSC-derived dopaminergic neuronal networks functionally impaired by low-concentrated MPP+. See our ISSCR 2015 poster on phenotypic prevention of functional MPP+ effects by GDNF using human iPSC-derived neurons.

Alpha-Synuclein Filaments show a disease relevant functional phenotype

Alpha-synuclein filaments influence the neuronal development of primary mouse midbrain cultures. We have optimized this approach so that a robust and reproducible read-out ensures the consistency of your results.

 

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Primary midbrain cultures treated at day 7, 14 and 18-21, change functional spike train parameters from microelectrode recordings significantly.

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For your screening project, we deliver the most relevant screening assay. Discuss with our experts your needs, so that we can deliver an appealing proposal.

So you can select between human and mouse cultures, different disease provoking compounds, or different genetic mutations or patient cell lines.

Comparing results from different models increases your predictive power dramatically.

 

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