Description
Studying α–synuclein (α-s) pathology and its effects on neuronal functionality is essential for understanding the mechanisms underlying the development and progression of Parkinson’s Disease (PD). Earlier functional and structural changes, such as the reduction of synaptic proteins, progressive impairments in neuronal excitability, synaptic activity, and network connectivity, have been reported with α–s aggregation in neuronal cells.In this study, we utilized an engineered circular tripartite neuronal network model integrated with microelectrode arrays (MEAs) as a platform to study functional markers during α-s aggregation and propagation. We focused on human induced pluripotent stem cell (hiPSC)-derived neuronal cultures. A gradual aggregation of α-s in conventional cultures and in the proximal compartments of circular tripartite networks was achieved after exposing neurons to fibrillar forms of α-s (PFFs). The axonal propagation of aggregated α-s to the distal networks was revealed while MEA recordings were collected from proximal and distal networks and assessed spatiotemporally. Additionally, for parallel functional assessment, calcium and mitochondrial readouts obtained from conventional single culture wells were analyzed for the same time points. We observed the impacts of α-s aggregation on both spontaneous neuronal activity and glutamatergic receptor channel-mediated neuronal activity, while calcium and mitochondrial functionality exhibited more complex patterns.
Our platform enabled the assessment of the early, middle, and late phases of α-s aggregation and propagation over a 13-day follow-up period. Alterations in protein expression, along with structural and functional changes at the cellular level in neuronal cultures, suggest a complex interplay during in vitro propagation of α-s aggregates. The suggested platform has the potential to be used in future pharmacological studies by enabling distinct treatment locations for preventive and therapeutic medications within studied networks.
| Aikajakso | 8 huhtik. 2024 |
|---|---|
| Tapahtuman otsikko | MxW Summit 2024 |
| Tapahtuman tyyppi | Conference |
| Sijainti | Zurich, SveitsiNäytä kartalla |
| Tunnustuksen arvo | International |