Background

Sex plays an important yet often underexplored role in neurodevelopment and neurotoxicity. While several studies report the importance of sex regarding anesthesia-induced neurotoxicity in neonatal mice, only few have focused on the late postnatal period. Here, to further understand the importance of sex regarding the neurobiological changes after early anesthesia during the critical synaptogenic period, we exposed postnatal day 16, 17 (PND 16, 17) mice to sevoflurane in pediatric patients and performed detailed evaluations in the hippocampus.

Methods

PND 16, 17 mice received a single exposure of oxygen with or without sevoflurane (2.5%) for 2 h. Changes of the hippocampus were analyzed in male and female mice 6 h after exposure: excitatory/inhibitory synaptic transmission, protein/mRNA expression levels of excitatory/inhibitory synaptic molecules (GluR1, GluR2, PSD95, gephyrin, GAD65), and number of excitatory synapses.

Results

Sevoflurane exposure increased the frequency of miniature excitatory postsynaptic currents specifically in male mice (control: 0.07 ± 0.04 [Hz]; sevoflurane: 14.72 ± 0.08 [Hz]), while miniature inhibitory postsynaptic currents were affected specifically in female mice. The protein/mRNA expression levels of excitatory synaptic molecules were also increased specifically in male mice. Unexpectedly, protein/mRNA expression levels of inhibitory synaptic molecules were increased in both sexes, and there was no male-specific increase of excitatory synapse number.

Conclusions

Exposure of mice to sevoflurane during the critical, late postnatal period induces sex-dependent changes in the hippocampus. Although often disregarded, our results confirm the importance of sex as a biological variable when studying the changes triggered by early anesthesia.

中文翻译：

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麻醉影响幼鼠海马关键突触形成期的兴奋性/抑制性突触：性别作为生物学变量的重要性

背景

性别在神经发育和神经毒性中起着重要但常常未被充分挖掘的作用。尽管有几项研究报告了性对于新生小鼠麻醉引起的神经毒性的重要性，但只有少数研究集中在产后后期。在这里，为了进一步了解性别对于关键突触形成期早期麻醉后神经生物学变化的重要性，我们将小儿患者的出生后第16、17天（PND 16、17）小鼠暴露于七氟醚中，并在海马体中进行了详细评估。

方法

PND 16、17只小鼠在有或没有七氟醚（2.5％）的情况下接受单次氧气暴露2小时。暴露后6 h，对雄性和雌性小鼠的海马变化进行了分析：兴奋性/抑制性突触传递，兴奋性/抑制性突触分子（GluR1，GluR2，PSD95，gephyrin，GAD65）的蛋白质/ mRNA表达水平以及兴奋性突触的数量。

结果

七氟醚暴露增加了微型兴奋性突触后电流的频率，特别是在雄性小鼠中（对照组：0.07±0.04 [Hz]；七氟醚：14.72±0.08 [Hz]），而微型抑制性突触后电流特别是在雌性小鼠中受到影响。雄性小鼠中兴奋性突触分子的蛋白质/ mRNA表达水平也特别增加。出乎意料的是，男女中抑制性突触分子的蛋白质/ mRNA表达水平均增加，并且兴奋性突触数量没有男性特异性的增加。

结论

小鼠在出生后的关键时期后期暴露于七氟醚中会引起海马的性别依赖性变化。尽管经常被忽视，但我们的结果证实了在研究早期麻醉引起的变化时，性别作为生物学变量的重要性。