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.
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 ligands such as GDNF is able to prevent the functional and morphological effects.
We offer this screening of neuro-protective 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.