GABAergic neurons are susceptible to BAX-dependent apoptosis following isoflurane exposure in the neonatal period.
GABAergic neurons are susceptible to BAX-dependent apoptosis following isoflurane exposure in the neonatal period.
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DOI：
10.1371/journal.pone.0238799
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Wright KM
中科院分区：
文献类型：
--
作者：
Slupe AM;Villasana L;Wright KM
在新生儿期暴露于挥发性麻醉药导致急性神经元死亡。先前的工作表明，细胞凋亡是介导神经元死亡的主要机制。我们发现，Bax缺乏症阻断神经元死亡后，暴露于异氟烷在新生儿期。阻断异氟烷介导的神经元死亡可减弱异氟烷暴露后小胶质细胞的神经炎症反应。我们发现GABA能中间神经元在垂死的神经元中不成比例地过多。尽管新生儿期异氟烷暴露诱导的神经元凋亡增加，但癫痫发作易感性、空间记忆保留和背景恐惧记忆在以后的生活中不受影响。然而，Bax缺陷单独导致空间记忆和情境恐惧记忆的轻度缺陷，表明正常发育性凋亡死亡对认知功能很重要。总的来说，这些结果表明，虽然新生儿大脑中的GABA能神经元在暴露于异氟烷后经历了升高的GABA依赖性凋亡细胞死亡，但这似乎不会对生命后期的整体神经功能产生长期影响。
Exposure to volatile anesthetics during the neonatal period results in acute neuron death. Prior work suggests that apoptosis is the dominant mechanism mediating neuron death. We show that Bax deficiency blocks neuronal death following exposure to isoflurane during the neonatal period. Blocking Bax-mediated neuron death attenuated the neuroinflammatory response of microglia following isoflurane exposure. We find that GABAergic interneurons are disproportionately overrepresented among dying neurons. Despite the increase in neuronal apoptosis induced by isoflurane exposure during the neonatal period, seizure susceptibility, spatial memory retention, and contextual fear memory were unaffected later in life. However, Bax deficiency alone led to mild deficiencies in spatial memory and contextual fear memory, suggesting that normal developmental apoptotic death is important for cognitive function. Collectively, these findings show that while GABAergic neurons in the neonatal brain undergo elevated Bax-dependent apoptotic cell death following exposure to isoflurane, this does not appear to have long-lasting consequences on overall neurological function later in life.
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