Research Paper Volume 13, Issue 11 pp 15569—15579
Repressor element-1 silencing transcription factor regulates glutamate receptors and immediate early genes to affect synaptic plasticity
- 1 Department of Neurology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
- 2 Gordon F. Derner School of Psychology, Adelphi University, New York, NY 11530-0701, USA
Received: January 26, 2021 Accepted: May 17, 2021 Published: June 9, 2021https://doi.org/10.18632/aging.203118
How to Cite
Copyright: © 2021 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: This study aimed to investigate the regulatory effects of repressor element-1 silencing transcription factor (REST) on the glutamate receptors and immediate early genes (IEGs) in the SH-SY5Y cells.
Methods: The genes regulated by REST were screened by bioinformatics between AD patients and the control group. Then, SH-SY5Y cells were treated with 10 μM Aβ or REST siRNA/cDNA, and the expressions of synaptic genes and IEGs were detected. Moreover, the protein expression of synaptophysin and PSD-95 was detected by Western blotting in the primary mouse hippocampal neurons.
Results: Firstly, 464 differentially expressed genes regulated by REST were identified between Alzheimer’s disease (AD) patients and controls, and REST was closely related to the glutamatergic synapses and long-term potentiation. GRIA1, GRIN2A, GRIN1, and ARC showed significant variations with the changes of REST. Moreover, the loss of REST reduced the expression of synaptophysin and PSD-95, which was related to synaptic plasticity.
Conclusion: REST maintains synaptic plasticity by affecting both glutamate receptors and IEGs, and the imbalance between neural excitation and inhibition mediated by REST compromises neural function, contributing to cognitive impairment.