The primary neuronal cells are more resistant than PC12 cells to α-synuclein toxic aggregates

Background: Alpha-synuclein (αSN) is an abundant presynaptic brain protein that its aggregated species believed to play pivotal roles in the development of neurodegenerative diseases, especially Parkinson's disease (PD). In this study, we compared the response of primary neuronal cells with a well-known cell line model, PC12, against the toxic aggregates of αSN.

Methods: Primary hippocampal neurons (PHNs) were isolated from 17 to 18 days old rat embryos. Fibrillization was induced in recombinant αSN and monitored by standard methods. The toxicity of different aggregates of αSN on the treated cells was then studied. Furthermore, changes in the intracellular reactive oxygen species (ROS) and Ca²⁺ levels were also compared in two kinds of treated cells. We also studied the gene expression profile of certain Ca²⁺ channels and carriers using the GEO2 database.

Results: The viability rate was significantly lower in PC12 versus PHNs, in response to αSN. This is while the intracellular ROS and Ca²⁺ levels were significantly increased in both cell types. Analysis of microarray data indicated that some factors involved in Ca²⁺ hemostasis may face significant changes in the PD condition.

Conclusion: By putting these data together, it is clear that PHN is more resistant than PC12 toward αSN cytotoxicity even in the presence of rising cytoplasmic ROS and Ca²⁺ levels. Exploring the supporting mechanisms which PHN uses to be more resistant to αSN cytotoxicity can help to open a roadmap toward therapeutic plans in PD and other synucleinopathy disorders.