小柯机器人

德国慕尼黑大学Mario M. Dorostkar和Jochen Herms团队合作发现，长期地西泮治疗导致线粒体18 kDa易位蛋白 (TSPO) 增强小胶质细胞脊柱吞噬并损害认知能力。相关论文于2022年2月28日发表于国际顶尖学术期刊《自然—神经科学》杂志上。

研究人员报告，地西泮，一种广泛使用的苯二氮卓类药物，会损害树突棘的结构可塑性，导致小鼠认知障碍。地西泮通过线粒体18kDa TSPO诱导这些缺陷，而不是通过改变小胶质细胞形态和突触物质吞噬作用的经典 γ-氨基丁酸 A 型受体。总的来说，研究结果证明了TSPO配体改变突触可塑性并因此导致认知障碍的机制。

据悉，苯二氮卓类药物被广泛用于治疗焦虑和失眠。除了耐受性发展和滥用倾向外，长期使用它们可能会导致认知障碍并增加痴呆症的风险。然而，苯二氮卓类药物可能导致持续认知能力下降的机制仍然未知。

附：英文原文

Title: Long-term diazepam treatment enhances microglial spine engulfment and impairs cognitive performance via the mitochondrial 18 kDa translocator protein (TSPO)

Author: Shi, Yuan, Cui, Mochen, Ochs, Katharina, Brendel, Matthias, Strbing, Felix L., Briel, Nils, Eckenweber, Florian, Zou, Chengyu, Banati, Richard B., Liu, Guo-Jun, Middleton, Ryan J., Rupprecht, Rainer, Rudolph, Uwe, Zeilhofer, Hanns Ulrich, Rammes, Gerhard, Herms, Jochen, Dorostkar, Mario M.

Issue&Volume: 2022-02-28

Abstract: Benzodiazepines are widely administered drugs to treat anxiety and insomnia. In addition to tolerance development and abuse liability, their chronic use may cause cognitive impairment and increase the risk for dementia. However, the mechanism by which benzodiazepines might contribute to persistent cognitive decline remains unknown. Here we report that diazepam, a widely prescribed benzodiazepine, impairs the structural plasticity of dendritic spines, causing cognitive impairment in mice. Diazepam induces these deficits via the mitochondrial 18kDa translocator protein (TSPO), rather than classical γ-aminobutyric acid type A receptors, which alters microglial morphology, and phagocytosis of synaptic material. Collectively, our findings demonstrate a mechanism by which TSPO ligands alter synaptic plasticity and, as a consequence, cause cognitive impairment.

DOI: 10.1038/s41593-022-01013-9

Source: https://www.nature.com/articles/s41593-022-01013-9

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