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https://nccur.lib.nccu.edu.tw/handle/140.119/160163
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| Title: | A new perspective on betaine: Targeting the glycine binding site of the NMDA receptor |
| Authors: | 詹銘煥
Chan, Ming-Huan;Chang, Wei-Tang;Lee, Mei-Yi;Wang, Ya-Jean;Huang, Wei-Cheng;Hsiesh, Chung-Ping;Tung, Chun-Wei;Chan, Ming-Huan;Chen, Hwei-Hsien |
| Contributors: | 神科所 |
| Keywords: | Calcium image;Glutamate;Glycine;GluN2A;GluN2B;GluN2C |
| Date: | 2025-12 |
| Issue Date: | 2025-11-13 10:59:08 (UTC+8) |
| Abstract: | Betaine, a methylated glycine derivative, shows promise in treating neuropsychiatric and neurological disorders, but its mechanisms remain unclear. This study investigates betaine’s concentration-dependent effects on NMDA receptor-mediated excitatory field potentials (EFPs) in mouse medial prefrontal cortex slices and calcium influx in cultured cortical neurons. We further assessed subtype specificity using HEK293 cells stably expressing GluN1/GluN2A, GluN1/GluN2B, or GluN1/GluN2C NMDA receptor subtypes, measuring calcium flux and single-channel activity. In cortical slices, betaine alone did not alter EFPs but, when co-applied with glutamate, significantly increased EFP frequency and amplitude. Conversely, co-application with glutamate and glycine markedly reduced EFPs. Similarly, in cultured cortical neurons, betaine enhanced NMDA receptor-dependent calcium influx with glutamate alone but attenuated it when both glutamate and glycine were present. In HEK293 cells, betaine exhibited dual modulatory effects on NMDA receptor-mediated calcium influx, varying with GluN2 subtype and glutamate/glycine concentrations. Cell-attached patch-clamp recordings confirmed that betaine with glutamate induced NMDA receptor currents, which were reduced by glycine co-application. Molecular docking and dynamics simulations proposed that betaine binds effectively to the glycine-binding site on the GluN1 subunit, with stable interactions. These findings identify betaine as a context-dependent modulator of NMDA receptors via its interaction with the glycine-binding site, offering a novel mechanism that may underlie its therapeutic potential in disorders involving NMDA receptor dysfunction. |
| Relation: | Biochemical Pharmacology, No.242, No.3, 117213 |
| Data Type: | article |
| DOI 連結: | https://doi.org/10.1016/j.bcp.2025.117213 |
| DOI: | 10.1016/j.bcp.2025.117213 |
| Appears in Collections: | [神經科學研究所] 期刊論文
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