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Increasing the interval between repeated anesthetic exposures reduces long-lasting synaptic changes in late post-natal mice.
Journal of Neurochemistry ( IF 4.2 ) Pub Date : 2020-07-08 , DOI: 10.1111/jnc.15121 Xianshu Ju 1, 2, 3 , Jianchen Cui 1, 2, 3 , Yulim Lee 1, 2, 3 , Sangil Park 4 , Boohwi Hong 4, 5 , Sungho Yoo 4 , Yoon Hee Kim 4, 5 , Youngkwon Ko 4, 5 , Chaeseong Lim 4, 5 , Sun Yeul Lee 4, 5 , Gi Ryang Kweon 1, 2 , Jun Young Heo 1, 2 , Woosuk Chung 1, 4, 5
Journal of Neurochemistry ( IF 4.2 ) Pub Date : 2020-07-08 , DOI: 10.1111/jnc.15121 Xianshu Ju 1, 2, 3 , Jianchen Cui 1, 2, 3 , Yulim Lee 1, 2, 3 , Sangil Park 4 , Boohwi Hong 4, 5 , Sungho Yoo 4 , Yoon Hee Kim 4, 5 , Youngkwon Ko 4, 5 , Chaeseong Lim 4, 5 , Sun Yeul Lee 4, 5 , Gi Ryang Kweon 1, 2 , Jun Young Heo 1, 2 , Woosuk Chung 1, 4, 5
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While recent studies strongly suggest that a single, short anesthetic exposure does not affect neurodevelopment, the effects of multiple exposures remain unclear. Unfortunately, studying “multiple exposures” is challenging as it is an extremely heterogeneous descriptor comprising diverse factors. One potentially important, but unrecognized factor is the interval between anesthetic exposures. In order to evaluate the significance of interval, we exposed post‐natal day 16, 17 mice to three sevoflurane exposures (2.5%, 1 hr) with short (2 hr) or long (24 hr) intervals. Changes in synaptic transmission, plasticity, protein expression, and behavior were assessed in male and female mice. We discovered that short‐interval exposures induced a female‐dependent decrease in miniature inhibitory post‐synaptic current (mIPSC) frequency 5 days after the last exposure (control: 18.44 ± 2.86 Hz, sevoflurane:14.65 ± 4.54 Hz). Short‐interval sevoflurane exposed mice also displayed long‐term behavioral deficits at adult age (hypoactivity, anxiety). These behavioral changes were consistent with the sex‐dependent changes in inhibitory transmission, as they were more robust in female mice. Although there was no change in learning and memory, short‐interval sevoflurane exposures also impaired LTP in a non‐sex‐dependent manner (control: 171.10 ± 26.90%, sevoflurane: 149.80 ± 26.48 %). Most importantly, we were unable to find long‐lasting consequences in mice that received long‐interval sevoflurane exposures. Our study provides novel insights regarding the significance of the interval between multiple exposures, and also suggests that the neurotoxic effects of multiple anesthetic exposures may be reduced by simply increasing the interval between each exposure.
中文翻译：
延长重复两次麻醉接触之间的间隔可减少出生后后期小鼠的长期突触变化。
尽管最近的研究强烈表明单次，短期麻醉暴露不会影响神经发育，但多次暴露的影响仍不清楚。不幸的是，研究“多重暴露”具有挑战性，因为它是一个包含多种因素的极其异类的描述词。一个潜在的重要但无法识别的因素是麻醉剂暴露之间的间隔。为了评估间隔的重要性，我们将出生后第16天，17天的小鼠以短（2小时）或长（24小时）间隔暴露于3次七氟醚暴露（2.5％，1小时）。在雄性和雌性小鼠中评估突触传递，可塑性，蛋白质表达和行为的变化。我们发现，短间隔暴露导致上次暴露后5天，女性依赖的微型抑制突触后电流（mIPSC）频率降低（对照：18.44±2.86 Hz，七氟醚：14.65±4.54 Hz）。短间隔暴露于七氟醚的小鼠在成年后也表现出长期的行为缺陷（机能减退，焦虑）。这些行为变化与抑制性传播中的性别依赖性变化一致，因为它们在雌性小鼠中更为牢固。尽管学习和记忆没有改变，但短间隔的七氟醚暴露也以非性别依赖性的方式损害了LTP（对照：171.10±26.90％，七氟醚：149.80±26.48％）。最重要的是，我们无法发现长期间隔接触七氟醚的小鼠具有长期的后果。
更新日期：2020-07-08
中文翻译：
延长重复两次麻醉接触之间的间隔可减少出生后后期小鼠的长期突触变化。
尽管最近的研究强烈表明单次，短期麻醉暴露不会影响神经发育，但多次暴露的影响仍不清楚。不幸的是，研究“多重暴露”具有挑战性，因为它是一个包含多种因素的极其异类的描述词。一个潜在的重要但无法识别的因素是麻醉剂暴露之间的间隔。为了评估间隔的重要性，我们将出生后第16天，17天的小鼠以短（2小时）或长（24小时）间隔暴露于3次七氟醚暴露（2.5％，1小时）。在雄性和雌性小鼠中评估突触传递，可塑性，蛋白质表达和行为的变化。我们发现，短间隔暴露导致上次暴露后5天，女性依赖的微型抑制突触后电流（mIPSC）频率降低（对照：18.44±2.86 Hz，七氟醚：14.65±4.54 Hz）。短间隔暴露于七氟醚的小鼠在成年后也表现出长期的行为缺陷（机能减退，焦虑）。这些行为变化与抑制性传播中的性别依赖性变化一致，因为它们在雌性小鼠中更为牢固。尽管学习和记忆没有改变，但短间隔的七氟醚暴露也以非性别依赖性的方式损害了LTP（对照：171.10±26.90％，七氟醚：149.80±26.48％）。最重要的是，我们无法发现长期间隔接触七氟醚的小鼠具有长期的后果。
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