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Abstract：
OBJECTIVE: The mechanism underlying the reversible unconsciousness induced by general anesthetics (GA) remains unclear. Recent studies revealed the critical roles of myelin and oligodendrocytes (OLs) in higher functions of the brain. However, it is unknown whether myelin actively participates in the regulation of GA. The aim of this study is to investigate the roles and possible mechanisms of myelin in the regulation of consciousness alterations induced by isoflurane anesthesia.
METHODS: First, demyelination models for the entire brain and specific neural nuclei were established to investigate the potential role of myelination in the regulation of GA, as well as its possible regional specificity. c-Fos staining was then performed on the demyelinated nuclei to verify the impact of myelin loss on neuronal activity. Finally, the activity of neurons during isoflurane anesthesia in demyelinated mice was recorded by optical fiber photometric calcium signal. The related behavioral indicators and EEG were recorded and analyzed.
RESULTS: A prolonged emergence time was observed from isoflurane anesthesia in demyelinated mice, which suggested the involvement of myelin in regulating GA. The demyelination in distinct nuclei by LPC further clarified the region-specific roles of isoflurane anesthesia regulation by myelin. The effect of demyelination on isoflurane anesthesia in the certain nucleus was consistent with that in neurons towards isoflurane anesthesia. Finally, we found that the mechanism of myelin in the modulation of isoflurane anesthesia is possibly through the regulation of neuronal activity.
CONCLUSIONS: In brief, myelin in the distinct neural nucleus plays an essential role in regulating the process of isoflurane anesthesia. The possible mechanism of myelin in the regulation of isoflurane anesthesia is neuronal activity modification by myelin integrity during GA. Our findings enhanced the comprehension of myelin function, and offered a fresh perspective for investigating the neural mechanisms of GA.
METHODS: First, demyelination models for the entire brain and specific neural nuclei were established to investigate the potential role of myelination in the regulation of GA, as well as its possible regional specificity. c-Fos staining was then performed on the demyelinated nuclei to verify the impact of myelin loss on neuronal activity. Finally, the activity of neurons during isoflurane anesthesia in demyelinated mice was recorded by optical fiber photometric calcium signal. The related behavioral indicators and EEG were recorded and analyzed.
RESULTS: A prolonged emergence time was observed from isoflurane anesthesia in demyelinated mice, which suggested the involvement of myelin in regulating GA. The demyelination in distinct nuclei by LPC further clarified the region-specific roles of isoflurane anesthesia regulation by myelin. The effect of demyelination on isoflurane anesthesia in the certain nucleus was consistent with that in neurons towards isoflurane anesthesia. Finally, we found that the mechanism of myelin in the modulation of isoflurane anesthesia is possibly through the regulation of neuronal activity.
CONCLUSIONS: In brief, myelin in the distinct neural nucleus plays an essential role in regulating the process of isoflurane anesthesia. The possible mechanism of myelin in the regulation of isoflurane anesthesia is neuronal activity modification by myelin integrity during GA. Our findings enhanced the comprehension of myelin function, and offered a fresh perspective for investigating the neural mechanisms of GA.
摘要：
目的：全身麻醉药（GA）引起可逆性失去知觉的潜在机制尚不清楚。最近的研究揭示了髓磷脂和少突胶质细胞（OL）在大脑的高级功能中的关键作用。然而,目前尚不清楚髓磷脂是否积极参与GA的调节。本研究的目的是探讨髓磷脂在异氟烷麻醉诱导的意识改变中的作用和可能的机制。
方法：首先，建立了全脑脱髓鞘和特定神经核的模型，以研究髓鞘形成在GA调节中的潜在作用，以及其可能的区域特异性。然后对脱髓鞘的细胞核进行c-Fos染色以验证髓鞘丢失对神经元活性的影响。最后,用光纤光度钙信号记录脱髓鞘小鼠异氟醚麻醉过程中神经元的活性。记录并分析相关行为指标和脑电图。
结果：在脱髓鞘小鼠中观察到异氟烷麻醉的出现时间延长，这表明髓磷脂参与调节GA。LPC在不同细胞核中的脱髓鞘进一步阐明了髓磷脂对异氟烷麻醉调节的区域特异性作用。脱髓鞘对异氟烷麻醉在某些核中的作用与对异氟烷麻醉的神经元中的作用一致。最后,我们发现髓鞘在异氟醚麻醉过程中的作用机制可能是通过调节神经元的活动。
结论：简而言之，不同神经核中的髓磷脂在异氟烷麻醉过程中起着至关重要的作用。髓鞘素调节异氟醚麻醉的可能机制是GA期间髓鞘素完整性对神经元活性的修饰。我们的发现增强了对髓鞘功能的理解，并为研究GA的神经机制提供了新的视角。
方法：首先，建立了全脑脱髓鞘和特定神经核的模型，以研究髓鞘形成在GA调节中的潜在作用，以及其可能的区域特异性。然后对脱髓鞘的细胞核进行c-Fos染色以验证髓鞘丢失对神经元活性的影响。最后,用光纤光度钙信号记录脱髓鞘小鼠异氟醚麻醉过程中神经元的活性。记录并分析相关行为指标和脑电图。
结果：在脱髓鞘小鼠中观察到异氟烷麻醉的出现时间延长，这表明髓磷脂参与调节GA。LPC在不同细胞核中的脱髓鞘进一步阐明了髓磷脂对异氟烷麻醉调节的区域特异性作用。脱髓鞘对异氟烷麻醉在某些核中的作用与对异氟烷麻醉的神经元中的作用一致。最后,我们发现髓鞘在异氟醚麻醉过程中的作用机制可能是通过调节神经元的活动。
结论：简而言之，不同神经核中的髓磷脂在异氟烷麻醉过程中起着至关重要的作用。髓鞘素调节异氟醚麻醉的可能机制是GA期间髓鞘素完整性对神经元活性的修饰。我们的发现增强了对髓鞘功能的理解，并为研究GA的神经机制提供了新的视角。
