Sustained effects of rapidly acting antidepressants require BDNF-dependent MeCP2 phosphorylation.

Autor: Kim JW; Department of Pharmacology, School of Medicine, Vanderbilt University, Nashville, TN, USA.; Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Autry AE; Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Na ES; Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Adachi M; Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Björkholm C; Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Kavalali ET; Department of Pharmacology, School of Medicine, Vanderbilt University, Nashville, TN, USA.; Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX, USA., Monteggia LM; Department of Pharmacology, School of Medicine, Vanderbilt University, Nashville, TN, USA. lisa.monteggia@vanderbilt.edu.; Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX, USA. lisa.monteggia@vanderbilt.edu.
Jazyk: angličtina
Zdroj: Nature neuroscience [Nat Neurosci] 2021 Aug; Vol. 24 (8), pp. 1100-1109. Date of Electronic Publication: 2021 Jun 28.
DOI: 10.1038/s41593-021-00868-8
Abstrakt: 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.
(© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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