| First Author | Kim JW | Year | 2021 |
| Journal | Nat Neurosci | Volume | 24 |
| Issue | 8 | Pages | 1100-1109 |
| PubMed ID | 34183865 | Mgi Jnum | J:323402 |
| Mgi Id | MGI:7263117 | Doi | 10.1038/s41593-021-00868-8 |
| Citation | Kim JW, et al. (2021) Sustained effects of rapidly acting antidepressants require BDNF-dependent MeCP2 phosphorylation. Nat Neurosci 24(8):1100-1109 |
| abstractText | The rapidly acting antidepressants ketamine and scopolamine exert behavioral effects that can last from several days to more than a week in some patients. The molecular mechanisms underlying the maintenance of these antidepressant effects are unknown. Here we show that methyl-CpG-binding protein 2 (MeCP2) phosphorylation at Ser421 (pMeCP2) is essential for the sustained, but not the rapid, antidepressant effects of ketamine and scopolamine in mice. Our results reveal that pMeCP2 is downstream of BDNF, a critical factor in ketamine and scopolamine antidepressant action. In addition, we show that pMeCP2 is required for the long-term regulation of synaptic strength after ketamine or scopolamine administration. These results demonstrate that pMeCP2 and associated synaptic plasticity are essential determinants of sustained antidepressant effects. |
