Parkinson’s-on-Chip Model: Screening the activity and its propagation of hPSC-derived neurons during α-synuclein aggregation on MEA embedded microfluidic chips

A well-known pathological feature of Parkinson’s disease (PD) is the accumulation of misfolded assemblies of a specific protein, i.e., α–synuclein. In PD, the pathologic α–synuclein assemblies can spread along the interconnected neuronal networks (circuits) in a "prion-like" manner promoting the spread of pathology [1,2]. Aggregated forms of α–synuclein travel through the axons anterogradely or retrogradely [3]. The formed malicious strains of α–
synuclein are also transferred to other neurons via different routes in which they behave as seeds to initiate the same pathological process. Recently, to initiate this cascade, preformed α–synuclein amyloid fibrils (PFFs) are used as seeds in several in vivo and in vitro studies [4]. Previously, the effects of extracellularly added α–synuclein monomers [5] and PFFs [6] on the neuronal spontaneous firing and Ca2+ oscillations were observed to cause reduced synaptic functionality.
Parkinson’s-on-chip model is an ongoing multidisciplinary project introducing the state-of-the-art tools from the cell biology, sensory technologies, microfluidics and biomedical signalanalysis to obtain novel information in synucleopathies, particularly in PD. In the project, previously developed custom chip models are utilized [7,8]. MEMO chip used in the project
has 3 separate compartments each of which has 24 electrodes. Tunnels between the compartments have also 8 electrodes each. Thus, both axonal and neuronal network level (dys)functionality are monitored and temporally defined in relation to disease progression. An example work from the project which utilizes MEMO chip [7] is described in Figure 1.