Lipid levels correlate with neuronal and dopaminergic markers during the differentiation of SH-SY5Y cells

Parkinson’s Disease (PD) is characterized by the loss of dopaminergic neurons and the deposition in the remaining cells of protein inclusions called Lewy Bodies (LBs). LBs are heterogeneous structures composed of protein and lipid molecules and their main constituent is the presynaptic protein α-synuclein. SH-SY5Y cells are neuroblastoma cells commonly used to model PD because they express dopaminergic markers and α-synuclein and they can be differentiated into neuronal cells using established protocols. Despite increasing evidence pointing towards a role of lipids in the initiation of PD, limited knowledge is available on the lipidome of undifferentiated and differentiated SH-SY5Y cells. In this study, we show that the levels and chemical properties of negatively charged phospholipids, diacyl glycerol and sphingolipids are specifically altered along the differentiation process of SH-SY5Y cells and that the levels of these lipids’ species correlate with those of dopaminergic and neuronal markers. These results are supported by proteomic data showing that the main biological processes affected by the differentiation of SH-SY5Y cells are lipid metabolism and processes associated with neuron maturation. Finally, our results show that electrophysiological activity can be detected in differentiated SH-SY5Y cells at a stage where most of the lipid changes have reached their maximal value. These results provide the first complete and quantitative characterisation of the changes in lipidome associated with the differentiation of SH-SY5Y cells into more neuronal and dopaminergic-like phenotype and serve as a basis for further characterisation of lipid disruptions in association with PD and its risk factors in this dopaminergic-like neuronal cell model.