Anesthesia affects excitatory/inhibitory synapses during the critical synaptogenic period in the hippocampus of young mice: Importance of sex as a biological variable

被引：15

作者：

Ju, Xianshu ^{[1
]}

Jang, Yunseon ^{[2
]}

Heo, Jun Young ^{[1
,2
]}

Park, Jiho ^{[3
,4
]}

Yun, Sangwon ^{[3
,4
]}

Park, Sangil ^{[4
]}

Huh, Yang Hoon ^{[5
]}

Kim, Hyo-Jeong ^{[5
]}

Lee, Yulim ^{[1
]}

Kim, Yoon Hee ^{[3
,4
]}

Lim, Chae Seong ^{[3
,4
]}

Lee, Sun Yeul ^{[3
,4
]}

Ko, Youngkwon ^{[3
,4
]}

Kweon, Gi Ryang ^{[2
]}

Chung, Woosuk ^{[1
,3
,4
]}

机构：

[1] Chungnam Natl Univ, Sch Med, Dept Med Sci, Daejeon, South Korea

[2] Chungnam Natl Univ, Sch Med, Dept Biochem, Daejeon, South Korea

[3] Chungnam Natl Univ, Sch Med, Dept Anesthesia & Pain Med, Daejeon, South Korea

[4] Chungnam Natl Univ Hosp, Dept Anesthesia & Pain Med, Daejeon, South Korea

[5] Korea Basic Sci Inst, Ctr Electron Microscopy Res, Cheongju, Chungcheongbukd, South Korea

来源：

NEUROTOXICOLOGY | 2019年 / 70卷

基金：

新加坡国家研究基金会;

关键词：

Anesthesia; General; Child development; Sex; SYNAPTIC-TRANSMISSION; SEVOFLURANE EXPOSURE; ASSOCIATION; CHILDREN; MEMORY; NEUROSCIENCE; IMPAIRMENT; BEHAVIOR; FETAL; RATS;

D O I：

10.1016/j.neuro.2018.11.014

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 post-synaptic 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.

引用

页码：146 / 153

页数：8