Functional Expression of NMDA Receptors in SH-SY5Y Neuroblastoma Cells Following Long-Term RA/BDNF-Induced Differentiation

Ya-Jean Wang; Yun-Hsiang Chen; Eric Hwang; Che-Jui Yeh; You-Xuan Liu; Hwei-Hsien Chen; Sheng-Nan Wu

doi:10.3390/neurosci6020047

Functional Expression of NMDA Receptors in SH-SY5Y Neuroblastoma Cells Following Long-Term RA/BDNF-Induced Differentiation

NeuroSci. 2025 May 26;6(2):47. doi: 10.3390/neurosci6020047.

Authors

Ya-Jean Wang¹, Yun-Hsiang Chen^{2

3}, Eric Hwang^{4

5

6}, Che-Jui Yeh⁴, You-Xuan Liu⁵, Hwei-Hsien Chen^{3

7}, Sheng-Nan Wu^{8

9}

Affiliations

¹ Department of Senior Services Industry Management, Minghsin University of Science and Technology, Hsinchu 30401, Taiwan.
² Department of Life Science, Fu-Jen Catholic University, New Taipei City 242062, Taiwan.
³ Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli 35053, Taiwan.
⁴ Institute of Molecular Medicine and Bioengineering, National Yang Ming Chiao Tung University, Hsinchu 300093, Taiwan.
⁵ Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu 300093, Taiwan.
⁶ Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu 300093, Taiwan.
⁷ Institute of Neuroscience, National Chengchi University, Taipei 116011, Taiwan.
⁸ Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan 70101, Taiwan.
⁹ Department of Medical Research and Education, An Nan Hospital, China Medical University Hospital, China Medical University, Tainan 709204, Taiwan.

Abstract

SH-SY5Y neuroblastoma cells can be effectively differentiated into a neuronal phenotype using retinoic acid (RA) and brain-derived neurotrophic factor (BDNF), making them a valuable in vitro model for studying neuronal differentiation. This study aimed to investigate the electrophysiological properties of SH-SY5Y cells following prolonged differentiation, with a focus on membrane characteristics, evoked action potentials, and the functionality of cellular components such as N-methyl-D-aspartate (NMDA) receptor. Whole-cell patch-clamp recordings were employed to evaluate ionic currents and action potentials in embryonic mouse cortical neurons (mCNs) and in both differentiated and undifferentiated SH-SY5Y neuroblastoma cells. Differentiated SH-SY5Y cells exhibited neurite outgrowth, evoked action potential firing, and functional NMDA receptor-mediated currents. Notably, atorvastatin significantly modulated the duration and firing of action potentials as well as NMDA receptor-mediated currents in differentiated SH-SY5Y cells. These findings highlight that neuronally differentiated SH-SY5Y cells expressing functional NMDA receptor-mediated currents serve as a robust and convenient model for investigating the molecular mechanisms of NMDA receptor function and for screening pharmacological agents targeting these receptors.

Keywords: NMDA receptor-mediated current; SH-SY5Y cells; atorvastatin; differentiation; evoked action potential.

Abstract

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