小柯机器人

2021年6月28日出版的《自然-神经科学》杂志发表了美国范德比尔特大学Lisa M. Monteggia研究小组的最新成果，他们的研究发现BDNF依赖的MeCP2磷酸化有利于抗抑郁药物持续发挥作用。

研究人员发现甲基CpG结合蛋白2 (MeCP2) 421位Ser的磷酸化（pMeCP2）对于氯胺酮和东莨菪碱在小鼠中发挥持续而非快速抗抑郁作用至关重要。研究表明pMeCP2位于BDNF 的下游，BDNF是氯胺酮和东莨菪碱抗抑郁作用的关键调控因子。

此外，研究表明pMeCP2是氯胺酮或东莨菪碱给药后长期调节突触强度所必需的。这些结果表明pMeCP2和相关的突触可塑性是持续抗抑郁作用的重要决定因素。

据介绍，速效抗抑郁药氯胺酮和东莨菪碱对某些患者的行为影响可持续数天至一周以上。但维持这些抗抑郁药物长效作用的分子机制尚不清楚。

附：英文原文

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

Author: Ji-Woon Kim, Anita E. Autry, Elisa S. Na, Megumi Adachi, Carl Bjrkholm, Ege T. Kavalali, Lisa M. Monteggia

Issue&Volume: 2021-06-28

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. How ketamine and scopolamine produce sustained antidepressant effects remains unknown. Kim et al. show that BDNF-dependent MeCP2 phosphorylation drives sustained antidepressant effects of ketamine and scopolamine with distinct synaptic plasticity changes.

DOI: 10.1038/s41593-021-00868-8

Source: https://www.nature.com/articles/s41593-021-00868-8

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex