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

Chang, Enqiang; Wang, Yangyang; Zhu, Ruilou; Wu, Lingzhi; Yang, Yulin; Zeng, Shuang; Li, Ningtao; Ruan, Xiaoguo; Sun, Menghong; Zhang, Wei; Zhou, Jun; Miao, Mengrong; Zhi, Hui; Zhao, Hailin; Chen, Qian; Sun, Qizhe; Chang, Emer; Chang, Albert; Zhang, Tingting; He, Xinfang; Liu, Kan; Ma, Song-Ya; Wang, Zhu; Zhang, Youming; Magnani, Luca; Ma, Ding; Zhang, Jiaqiang

doi:10.1016/j.isci.2023.106534

Cited by 7 publications

(6 citation statements)

References 52 publications

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“…Previous study indicated that both propofol and sevoflurane had substantial and transient effects on the transcriptome profiles of microglia, excitatory neurons, interneurons, astrocytes, and oligodendrocyte progenitor cells, showed that clinically relevant doses of both propofol and sevoflurane promoted "microgliosis, " but only sevoflurane induced significant alterations in microglial gene expression patterns (Chang et al, 2023). Our study used snRNA-seq in rhesus macaques and compared the data with publicly available human embryonic data from databases, aims to help explain the potential neurotoxicity induced by general anesthetics and provide a blueprint for future mechanistic studies of anesthetics, which shares 10.…”

Section: Discussionmentioning

confidence: 99%

“…Previous publication also conducted KEGG pathway analysis of differently expressed genes in inhibitory neurons after sevoflurane exposure. The results indicated that differently expressed genes were enriched in pathways related to WNT signaling pathway, viral carcinogenesis, and platelet activation, after 6 h of sevoflurane anesthesia (Chang et al, 2023). Notably, the WNT signaling pathway plays a crucial role in the nervous system, exerting significant influence on neuronal development and synaptic formation (Lv et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

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Inhibitory neuron map of sevoflurane induced neurotoxicity model in young primates

Niu,

Cheng,

Miao

et al. 2023

Front. Cell. Neurosci.

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IntroductionSevoflurane, one of the most commonly used anesthetic agents in children, may induce neuronal dysfunction and cognitive impairment. Exposure to sevoflurane might induce an imbalance between neural excitation and inhibition which could be a mechanism behind anesthesia-induced cognitive and affective dysfunctions. However, the underlying mechanisms remain unclear.MethodsIn this study, we used two rhesus macaques in the control group, and one rhesus macaques in the anesthesia group. We employed single-nucleus RNA sequencing (snRNA-seq) technology to explore alterations in distinct types of inhibitory neurons involved in the long-term cognitive impairment caused by sevoflurane in young macaques.ResultsFollowing sevoflurane treatment, an upregulation was observed in the SST+ inhibitory neuron in the LHX6+ neighborhood in the hippocampus of rhesus macaques. This alteration might impact brain development by influencing interneuron migration and maturation. Additionally, we proposed a novel classification of inhibitory neurons, defined by CNR1 and LHX6 applicable to both humans and macaques.DiscussionOur study proposed a novel classification of inhibitory neurons defined by LHX6 and CNR1, relevant in macaques and humans. We also provide evidence that sevoflurane upregulated the SST+ inhibitory neuron in the LHX6+ neighborhood in the hippocampus of rhesus macaques, which may underlie the potential neurotoxic effects induced by general anesthetics. Our results also offer a more reliable approach for studying the structure and function of the human brain.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inhibitory neuron map of sevoflurane induced neurotoxicity model in young primates

Niu,

Cheng,

Miao

et al. 2023

Front. Cell. Neurosci.

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“…Microglia are regulated by clinical doses of GAAs. In human fetal prefrontal cortex mixed cell cultures, clinically relevant doses/concentrations of both propofol (20 μΜ, 6 h) and sevoflurane (3.3%, 6 h) promoted "microgliosis", and sevoflurane also reduced microglial transcription [ 12 ]. The use of GAAs is an important risk factor for perioperative neurocognitive dysfunction (PND) because the microglial activation and neuroinflammation caused by GAAs plays an important role in the pathogenesis of PND [ 13 ].…”

Section: Evidence From Preclinical Studiesmentioning

confidence: 99%

Effect of General Anesthetic Agents on Microglia

Yang,

Hang,

et al. 2023

Aging and disease

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The effects of general anesthetic agents (GAAs) on microglia and their potential neurotoxicity have attracted the attention of neuroscientists. Microglia play important roles in the inflammatory process and in neuromodulation of the central nervous system. Microglia-mediated neuroinflammation is a key mechanism of neurocognitive dysfunction during the perioperative period. Microglial activation by GAAs induces anti-inflammatory and pro-inflammatory effects in microglia, suggesting that GAAs play a dual role in the mechanism of postoperative cognitive dysfunction. Understanding of the mechanisms by which GAAs regulate microglia may help to reduce the incidence of postoperative adverse effects. Here, we review the actions of GAAs on microglia and the consequent changes in microglial function. We summarize clinical and animal studies associating microglia with general anesthesia and describe how GAAs interact with neurons via microglia to further explore the mechanisms of action of GAAs in the nervous system.

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“…Sevoflurane, also known as fluoromethyl hexafluoroisopropyl ether, is a ubiquitous general anesthetic agent extensively employed in contemporary clinical practice. 1,2 A multitude of investigations have been conducted to elucidate neural signal dynamics under sevoflurane anesthesia. 3,4 Nevertheless, emerging studies underscore the potential adverse consequences associated with sevoflurane, including nerve impairment and cognitive deficiency.…”

mentioning

confidence: 99%

“…Sevoflurane, also known as fluoromethyl hexafluoroisopropyl ether, is a ubiquitous general anesthetic agent extensively employed in contemporary clinical practice. , A multitude of investigations have been conducted to elucidate neural signal dynamics under sevoflurane anesthesia. , Nevertheless, emerging studies underscore the potential adverse consequences associated with sevoflurane, including nerve impairment and cognitive deficiency. , Consequently, medical practitioners must maintain vigilant post sevoflurane anesthesia surveillance of the patients’ conditions, necessitating significant time and effort during the recovery of consciousness. In addition, intraoperative arousal has proven indispensable for numerous medical conditions, such as Parkinson’s disease, offering critical assistance to doctors during surgery. , Hence, precise assessment of the awareness state during sevoflurane anesthesia, along with application of timely intraoperative wake-up tests, is essential.…”

mentioning

confidence: 99%

High-Performance Bidirectional Microelectrode Array for Assessing Sevoflurane Anesthesia Effects and In Situ Electrical Stimulation in Deep Brain Regions

Jia,

Duan,

Liu

et al. 2024

ACS Sens.

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Precise assessment of wakefulness states during sevoflurane anesthesia and timely arousal are of paramount importance to refine the control of anesthesia. To tackle this issue, a bidirectional implantable microelectrode array (MEA) is designed with the capability to detect electrophysiological signal and perform in situ deep brain stimulation (DBS) within the dorsomedial hypothalamus (DMH) of mice. The MEA, modified with platinum nanoparticles/IrOx nanocomposites, exhibits exceptional characteristics, featuring low impedance, minimal phase delay, substantial charge storage capacity, high double-layer capacitance, and longer in vivo lifetime, thereby enhancing the sensitivity of spike firing detection and electrical stimulation (ES) effectiveness. Using this MEA, sevoflurane-inhibited neurons and sevoflurane-excited neurons, together with changes in the oscillation characteristics of the local field potential within the DMH, are revealed as indicative markers of arousal states. During the arousal period, varying-frequency ESs are applied to the DMH, eliciting distinct arousal effects. Through in situ detection and stimulation, the disparity between these outcomes can be attributed to the influence of DBS on different neurons. These advancements may further our understanding of neural circuits and their potential applications in clinical contexts.

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

Cited by 7 publications

References 52 publications

Inhibitory neuron map of sevoflurane induced neurotoxicity model in young primates

Inhibitory neuron map of sevoflurane induced neurotoxicity model in young primates

Effect of General Anesthetic Agents on Microglia

High-Performance Bidirectional Microelectrode Array for Assessing Sevoflurane Anesthesia Effects and In Situ Electrical Stimulation in Deep Brain Regions

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