Negi, Deepika, Shorter, Susan, Goodhall, Iain, Razansky, Daniel, Shergil, Sukhi and Ovsepian, Saak V. (2025) Structural and molecular differentiation of cultured human neurons is accompanied by alterations of spontaneous and evoked calcium dynamics. Scientific Reports, 15:34196. ISSN 2045-2322 (Online) (doi:10.1038/s41598-025-15561-0)

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Abstract

During development, neuronal precursors transform from a pluripotent state into specialized neurons. While much research has been conducted into morphological and molecular changes, there is a pressing need to define accompanying functional alterations. We used immunofluorescence microscopy and live imaging in SH-SY5Y-derived human neurons to elucidate the relationship between structural and molecular differentiation with evoked and spontaneous Ca2+ dynamics. In the undifferentiated state expressing trace amounts of neuronal markers, SH-SY5Y cells maintain spontaneous high-amplitude slow Ca2+ oscillations, with their stimulation by carbochol activating low-amplitude Ca2+ transients. Driving SH-SY5Y cells into the 2CL state by retinoic acid facilitated the outgrowth of neurites and expression of neuron-specific proteins. These changes are accompanied by the abolition of Ca2+ oscillations. Differentiating SH-SY5Y cells into definitive neurons by a cocktail of retinoic acid and BDNF induced their polarization and enrichment with specific neuronal markers, accompanied by a resurgence of spontaneous Ca2+ oscillations but with faster kinetics. The carbachol-induced rise of Ca2+ in these cells showed a higher peak and biphasic decay. At all developmental stages, Ca2+ transients in response to ionomycin were indistinguishable. These findings lead us to conclude that a switch of Ca2+ dynamics accompanies structural and molecular differentiation of SH-SY5Y cell-derived human neurons, contributing to the developmental process.

Item Type:	Article
Uncontrolled Keywords:	neuroblastoma-derived neurons, BDNF, calcium imaging, spontaneous activity, molecular polarization, SH-SY5Y cells
Subjects:	Q Science > Q Science (General) Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI)
Last Modified:	12 Dec 2025 13:01
URI:	https://gala.gre.ac.uk/id/eprint/51945

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