Label-Free SERS Detection of Molecular Stress Response in the Golgi Apparatus Induced by Pulsed Electrical Stimulation during Neuronal Cell Differentiation.

Regulating neuronal cell differentiation in a controllable manner is crucial for the treatment of nervous system regeneration. In this study, we present a method utilizing pulsed electrical stimulation (PES) to accelerate the differentiation of SH-SY5Y cells and investigate the molecular stress response of the Golgi apparatus (GA) through SERS spectra. Compared with traditional drug stimulation (10 days), this simple PES approach within 2 days achieves a 5-fold increase in the rate of generating SH-SY5Y-derived neurons. PES-treated neuron cells showed an increased level of mature neuronal marker Tuj1 and increased expression of related genes Tubb3 and Eno2. We found that PES induces SH-SY5Y cell differentiation by regulating the expression of MAPK/ERK and calcium signaling pathway proteins. The GA-related changes in this pathway are shown by SERS spectra. In situ SERS shows that the content levels rise while lipid levels drop with prolonged differentiation. This work offers a new strategy for SH-SY5Y differentiation and insights into the GA molecular stress response.