@article{1ac30ff51a2c45d98fee8840a6e9401f,
title = "Sustained effects of rapidly acting antidepressants require BDNF-dependent MeCP2 phosphorylation",
abstract = "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.",
author = "Kim, {Ji Woon} and Autry, {Anita E.} and Na, {Elisa S.} and Megumi Adachi and Carl Bj{\"o}rkholm and Kavalali, {Ege T.} and Monteggia, {Lisa M.}",
note = "Funding Information: We thank members of the Monteggia and Kavalali laboratory for helpful advice and discussions on the manuscript. We thank K. Szabla for the initial insight into this project. We thank A. West for providing the initial pMeCP2 antibody for these studies. This work was supported by National Institutes of Health grants MH070727 and MH081060 (to L.M.M.) and MH066198 (to E.T.K.); the Basic Science Research Program through the National Research Foundation of Korea, funded by the Ministry of Education (2016R1A6A3A03008533, to J.K.); and postdoctoral fellowships from the Elisabeth and Alfred Ahlqvist Foundation within the Swedish Pharmaceutical Society and the Swedish Society for Medical Research (to C.B.). Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2021",
month = aug,
doi = "10.1038/s41593-021-00868-8",
language = "English (US)",
volume = "24",
pages = "1100--1109",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "8",
}