Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior.
Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior.
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新生小鼠长期接触七氟醚会导致小胶质细胞过度分化，减少小胶质细胞与突触之间的接触，并导致成年行为缺陷。
DOI：
10.3389/fneur.2023.1142739
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发表时间：
2023
影响因子：
3.4
通讯作者：
Chen, Lingmin
中科院分区：
文献类型：
--
作者：
Li, Hong;Zhou, Bin;Liao, Ping;Liao, Daqing;Yang, Linghui;Wang, Jing;Liu, Jin;Jiang, Ruotian;Chen, Lingmin
已知在发育过程中长时间接触全身麻醉剂会导致神经行为异常，但所涉及的细胞和分子机制尚不清楚。小胶质细胞是中枢神经系统中的常驻免疫细胞，在正常大脑发育中发挥着重要作用。在该研究中，出生后第 7 天 (P7) C57BL/6 小鼠被随机分配到两组。在七氟烷 (SEVO) 中，小鼠暴露于 2.5% 七氟烷 4 小时。对照组中，小鼠暴露于载气（30% O2/70% N2）4小时。对 P14 至 P21 小鼠的固定脑切片进行离子化钙结合接头分子 1 (IBA-1) 免疫标记，以可视化小胶质细胞。使用ImageJ和Imaris软件对体感皮层小胶质细胞进行形态学分析。采用串行块面扫描电子显微镜 (SBF-SEM) 来评估 P14 和 P21 小鼠小胶质细胞的超微结构以及小胶质细胞与突触之间的接触。对 P14 和 P21 小鼠的脑切片进行共聚焦成像，以评估静息和激活状态下的小胶质细胞监测。行为测试用于评估小胶质细胞消耗和再生对七氟醚暴露引起的神经行为异常的影响。新生小鼠长时间暴露于七氟烷会诱导小胶质细胞超分枝，暴露后 14 天，总分支长度、树枝化面积和分支复杂性增加。新生儿长时间暴露于七氟醚会减少小胶质细胞和突触之间的接触，但不会影响静息状态下小胶质细胞的监测或对激光引起的局灶性脑损伤的反应。新生儿小胶质细胞的这些变化与成年小鼠的焦虑样行为有关。此外，接触七氟醚之前小胶质细胞的消耗以及随后在新生儿大脑中的重新增殖减轻了七氟醚接触引起的焦虑样行为。我们的实验表明全身麻醉药可能会损害发育中的大脑，而小胶质细胞可能是全身麻醉相关发育神经毒性的重要目标。
Prolonged exposure to general anesthetics during development is known to cause neurobehavioral abnormalities, but the cellular and molecular mechanisms involved are unclear. Microglia are the resident immune cells in the central nervous system and play essential roles in normal brain development. In the study, postnatal day 7 (P7) C57BL/6 mice were randomly assigned to two groups. In the sevoflurane (SEVO), mice were exposed to 2.5% sevoflurane for 4 h. In the control group, mice were exposed to carrier gas (30% O2/70% N2) for 4 h. Fixed brain slices from P14 to P21 mice were immunolabeled for ionized calcium-binding adapter molecule 1 (IBA-1) to visualize microglia. The morphological analysis of microglia in the somatosensory cortex was performed using ImageJ and Imaris software. Serial block face scanning electron microscopy (SBF-SEM) was performed to assess the ultrastructure of the microglia and the contacts between microglia and synapse in P14 and P21 mice. The confocal imaging of brain slices was performed to assess microglia surveillance in resting and activated states in P14 and P21 mice. Behavioral tests were used to assess the effect of microglia depletion and repopulation on neurobehavioral abnormalities caused by sevoflurane exposure. The prolonged exposure of neonatal mice to sevoflurane induced microglia hyper-ramification with an increase in total branch length, arborization area, and branch complexity 14 days after exposure. Prolonged neonatal sevoflurane exposure reduced contacts between microglia and synapses, without affecting the surveillance of microglia in the resting state or responding to laser-induced focal brain injury. These neonatal changes in microglia were associated with anxiety-like behaviors in adult mice. Furthermore, microglial depletion before sevoflurane exposure and subsequent repopulation in the neonatal brain mitigated anxiety-like behaviors caused by sevoflurane exposure. Our experiments indicate that general anesthetics may harm the developing brain, and microglia may be an essential target of general anesthetic-related developmental neurotoxicity.
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影响因子：
34.7
作者：
Clarke, Laura E.;Barres, Ben A.
通讯作者：
Barres, Ben A.
DOI：
10.1016/s0140-6736(15)00608-x
发表时间：
2016-01-16
期刊：
Lancet (London, England)
影响因子：
--
作者：
Davidson AJ;Disma N;de Graaff JC;Withington DE;Dorris L;Bell G;Stargatt R;Bellinger DC;Schuster T;Arnup SJ;Hardy P;Hunt RW;Takagi MJ;Giribaldi G;Hartmann PL;Salvo I;Morton NS;von Ungern Sternberg BS;Locatelli BG;Wilton N;Lynn A;Thomas JJ;Polaner D;Bagshaw O;Szmuk P;Absalom AR;Frawley G;Berde C;Ormond GD;Marmor J;McCann ME;GAS consortium
通讯作者：
GAS consortium
影响因子：
9.8
作者：
Culley, D. J.;Cotran, E. K.;Crosby, G.
通讯作者：
Crosby, G.
影响因子：
9.8
作者：
Kang E;Jiang D;Ryu YK;Lim S;Kwak M;Gray CD;Xu M;Choi JH;Junn S;Kim J;Xu J;Schaefer M;Johns RA;Song H;Ming GL;Mintz CD
通讯作者：
Mintz CD
影响因子：
4.8
作者：
Arcuri C;Mecca C;Bianchi R;Giambanco I;Donato R
通讯作者：
Donato R