Equipe Synaptopathies et Autoanticorps (SynatAc), Institut NeuroMyoGène, INSERM U1217/UMR CNRS 5310, Lyon, France.
Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.
PLoS One. 2020 Aug 6;15(8):e0236594. doi: 10.1371/journal.pone.0236594. eCollection 2020.
Microglia, the resident immune cells of the brain, are highly ramified and motile and their morphology is strongly linked to their function. Microglia constantly monitor the brain parenchyma and are crucial for maintaining brain homeostasis and fine-tuning neuronal networks. Besides affecting neurons, anesthetics may have wide-ranging effects mediated by non-neuronal cells and in particular microglia. We thus examined the effect of two commonly used anesthetic agents, ketamine/xylazine and barbiturates, on microglial motility and morphology. A combination of two-photon in vivo imaging and electroencephalography (EEG) recordings in unanesthetized and anesthetized mice as well as automated analysis of ex vivo sections were used to assess morphology and dynamics of microglia. We found that administration of ketamine/xylazine and pentobarbital anesthesia resulted in quite distinct EEG profiles. Both anesthetics reduced microglial motility, but only ketamine/xylazine administration led to reduction of microglial complexity in vivo. The change of cellular dynamics in vivo was associated with a region-dependent reduction of several features of microglial cells ex vivo, such as the complexity index and the ramification length, whereas thiopental altered the size of the cytoplasm. Our results show that anesthetics have considerable effects on neuronal activity and microglial morphodynamics and that barbiturates may be a preferred anesthetic agent for the study of microglial morphology. These findings will undoubtedly raise compelling questions about the functional relevance of anesthetics on microglial cells in neuronal physiology and anesthesia-induced neurotoxicity.
小胶质细胞是大脑中的常驻免疫细胞，具有高度分支和运动性，其形态与其功能密切相关。小胶质细胞不断监测脑实质，对于维持脑内环境平衡和微调神经元网络至关重要。除了影响神经元外，麻醉剂可能通过非神经元细胞，特别是小胶质细胞，产生广泛的影响。因此，我们研究了两种常用麻醉剂（氯胺酮/甲苯噻嗪和巴比妥类药物）对小胶质细胞运动和形态的影响。我们使用双光子体内成像和脑电图（EEG）记录结合未麻醉和麻醉小鼠，以及对离体切片的自动分析，评估小胶质细胞的形态和动力学。我们发现，氯胺酮/甲苯噻嗪和戊巴比妥麻醉的给药导致了非常不同的 EEG 图谱。两种麻醉剂都降低了小胶质细胞的运动性，但只有氯胺酮/甲苯噻嗪给药导致体内小胶质细胞复杂性降低。体内细胞动力学的变化与体外小胶质细胞的几个特征的区域依赖性减少有关，如复杂性指数和分支长度，而硫喷妥钠改变了细胞质的大小。我们的结果表明，麻醉剂对神经元活动和小胶质细胞形态动力学有很大的影响，并且巴比妥类药物可能是研究小胶质细胞形态的首选麻醉剂。这些发现无疑将引发关于麻醉剂对神经元生理学和麻醉诱导神经毒性中小胶质细胞功能相关性的引人关注的问题。
