General anesthetic action profile on the human prefrontal cortex cells through comprehensive single-cell RNA-seq analysis

Enqiang Chang; Yangyang Wang; Ruilou Zhu; Lingzhi Wu; Yitian Yang; Shuang Zeng; Ningtao Li; Xiaoguo Ruan; Mingyang Sun; Wei Zhang; Jun Zhou; Mengrong Miao; Hui Zhi; Hailin Zhao; Qian Chen; Qizhe Sun; Emer Chang; Albert Chang; Tingting Zhang; Xinfang He; Kan Liu; Songhua Ma; Weizhong Zhu; Youming Zhang; Luca Magnani; Daqing Ma; Jiaqiang Zhang

doi:10.1016/j.isci.2023.106534

General anesthetic action profile on the human prefrontal cortex cells through comprehensive single-cell RNA-seq analysis

iScience. 2023 Mar 31;26(4):106534. doi: 10.1016/j.isci.2023.106534. eCollection 2023 Apr 21.

Authors

Enqiang Chang^{1

2}, Yangyang Wang¹, Ruilou Zhu¹, Lingzhi Wu², Yitian Yang¹, Shuang Zeng¹, Ningtao Li¹, Xiaoguo Ruan¹, Mingyang Sun¹, Wei Zhang¹, Jun Zhou¹, Mengrong Miao¹, Hui Zhi¹, Hailin Zhao², Qian Chen², Qizhe Sun², Emer Chang², Albert Chang², Tingting Zhang³, Xinfang He⁴, Kan Liu⁴, Songhua Ma⁵, Weizhong Zhu⁵, Youming Zhang⁶, Luca Magnani⁷, Daqing Ma^{2

8}, Jiaqiang Zhang¹

Affiliations

¹ Department of Anaesthesiology and Perioperative Medicine, Center for Clinical Single Cell Biomedicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
² Division of Anesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, UK.
³ Center for Clinical Single Cell Biomedicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
⁴ Department of Gynecology and Obstetrics, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
⁵ Department of Physiology, School of Medicine, Nantong University, Nantong, Jiangsu, China.
⁶ Section of Genomic and Environmental Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK.
⁷ Division of Cancer, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London UK.
⁸ National Clinical Research Center for Child Health, Zhejiang, China.

Abstract

The cellular and molecular actions of general anesthetics to induce anesthesia state and also cellular signaling changes for subsequent potential "long term" effects remain largely elusive. General anesthetics were reported to act on voltage-gated ion channels and ligand-gated ion channels. Here we used single-cell RNA-sequencing complemented with whole-cell patch clamp and calcium transient techniques to examine the gene transcriptome and ion channels profiling of sevoflurane and propofol, both commonly used clinically, on the human fetal prefrontal cortex (PFC) mixed cell cultures. Both propofol and sevoflurane at clinically relevant dose/concentration promoted "microgliosis" but only sevoflurane decreased microglia transcriptional similarity. Propofol and sevoflurane each extensively but transiently (<2 h) altered transcriptome profiling across microglia, excitatory neurons, interneurons, astrocytes and oligodendrocyte progenitor cells. Utilizing scRNA-seq as a robust and high-through put tool, our work may provide a comprehensive blueprint for future mechanistic studies of general anesthetics in clinically relevant settings.

Keywords: Neuroscience; Techniques in neuroscience; Transcriptomics.