小柯机器人

南方科技大学Xue-Jun Song团队近期取得重要工作进展，他们研究发现麻醉后的意识恢复是通过丘脑背内侧核中KCC2的泛素化降解实现的。相关研究成果2023年3月27日在线发表于《自然—神经科学》杂志上。

据介绍，麻醉后的意识恢复，曾经被认为是一个被动的过程，现在被认为是主动和可控的过程。

研究人员在小鼠中发现，当不同麻醉剂迫使大脑进入最低反应状态时，腹后内侧核（VPM）中K⁺/Cl⁻协同转运蛋白2（KCC2）的快速下调是大脑恢复意识的常见机制。泛素蛋白酶体降解负责KCC2的下调，这是由泛素连接酶Fbxl4驱动的。KCC2在Thr1007处的磷酸化促进KCC2和Fbxl4之间的相互作用。KCC2下调导致γ-氨基丁酸A型受体介导的去抑制，使VPM神经元兴奋性加速恢复，并使意识从麻醉抑制中出现。这种恢复途径是一个活跃的过程，与麻醉剂的选择无关。

总之，这一研究表明，VPM中KCC2的泛素化降解是麻醉后意识恢复的重要中间步骤。

附：英文原文

Title: Emergence of consciousness from anesthesia through ubiquitin degradation of KCC2 in the ventral posteromedial nucleus of the thalamus

Author: Hu, Jiang-Jian, Liu, Yuexin, Yao, Hongyu, Cao, Boxu, Liao, Huabao, Yang, Ruodi, Chen, Peng, Song, Xue-Jun

Issue&Volume: 2023-03-27

Abstract: The emergence of consciousness from anesthesia, once assumed to be a passive process, is now considered as an active and controllable process. In the present study, we show in mice that, when the brain is forced into a minimum responsive state by diverse anesthetics, a rapid downregulation of K+/Cl cotransporter 2 (KCC2) in the ventral posteromedial nucleus (VPM) serves as a common mechanism by which the brain regains consciousness. Ubiquitin-proteasomal degradation is responsible for KCC2 downregulation, which is driven by ubiquitin ligase Fbxl4. Phosphorylation of KCC2 at Thr1007 promotes interaction between KCC2 and Fbxl4. KCC2 downregulation leads to γ-aminobutyric acid type A receptor-mediated disinhibition, enabling accelerated recovery of VPM neuron excitability and emergence of consciousness from anesthetic inhibition. This pathway to recovery is an active process and occurs independent of anesthetic choice. The present study demonstrates that ubiquitin degradation of KCC2 in the VPM is an important intermediate step en route to emergence of consciousness from anesthesia.

DOI: 10.1038/s41593-023-01290-y

Source: https://www.nature.com/articles/s41593-023-01290-y

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