| dc.contributor | 神科所 | |
| dc.creator (作者) | 詹銘煥 | |
| dc.creator (作者) | 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 | |
| dc.date (日期) | 2025-12 | |
| dc.date.accessioned | 13-Nov-2025 10:59:08 (UTC+8) | - |
| dc.date.available | 13-Nov-2025 10:59:08 (UTC+8) | - |
| dc.date.issued (上傳時間) | 13-Nov-2025 10:59:08 (UTC+8) | - |
| dc.identifier.uri (URI) | https://nccur.lib.nccu.edu.tw/handle/140.119/160163 | - |
| dc.description.abstract (摘要) | 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. | |
| dc.format.extent | 105 bytes | - |
| dc.format.mimetype | text/html | - |
| dc.relation (關聯) | Biochemical Pharmacology, No.242, No.3, 117213 | |
| dc.subject (關鍵詞) | Calcium image; Glutamate; Glycine; GluN2A; GluN2B; GluN2C | |
| dc.title (題名) | A new perspective on betaine: Targeting the glycine binding site of the NMDA receptor | |
| dc.type (資料類型) | article | |
| dc.identifier.doi (DOI) | 10.1016/j.bcp.2025.117213 | |
| dc.doi.uri (DOI) | https://doi.org/10.1016/j.bcp.2025.117213 | |
