Perioperative Medicine  |   February 2017
Sevoflurane Exposure during the Critical Period Affects Synaptic Transmission and Mitochondrial Respiration but Not Long-term Behavior in Mice
Author Notes
  • From the Department of Anesthesia and Pain Medicine, Chungnam National University, Daejeon, South Korea (W.C., S.L., S.Y., S.P., Y.H.K., S.H.Y., Y.S.S., W.H.L., Y.K.); Departments of Biochemistry (M.J.R., J.Y.H., G.R.K.) and Medical Science (J.Y.H., X.J.), Chungnam National University School of Medicine, Daejeon, South Korea; and Departments of Biological Sciences (H.P.) and Biomedical Sciences (Y.K.), Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
  • This article is featured in “This Month in Anesthesiology,” page 1A.
    This article is featured in “This Month in Anesthesiology,” page 1A.×
  • Submitted for publication March 3, 2016. Accepted for publication October 28, 2016.
    Submitted for publication March 3, 2016. Accepted for publication October 28, 2016.×
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • W.C., M.J.R., and J.Y.H. contributed equally to this article.
    W.C., M.J.R., and J.Y.H. contributed equally to this article.×
  • Address correspondence to Dr. Ko: Department of Anesthesiology and Pain Medicine, Chungnam National University, School of Medicine, Daejeon 301-721, South Korea. annn8432@gmail.com. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Basic Science / Pharmacology
Perioperative Medicine   |   February 2017
Sevoflurane Exposure during the Critical Period Affects Synaptic Transmission and Mitochondrial Respiration but Not Long-term Behavior in Mice
Anesthesiology 2 2017, Vol.126, 288-299. doi:10.1097/ALN.0000000000001470
Anesthesiology 2 2017, Vol.126, 288-299. doi:10.1097/ALN.0000000000001470
Abstract

Background: Anesthesia during the synaptogenic period induces dendritic spine formation, which may affect neurodevelopment. The authors, therefore, evaluated whether changes in synaptic transmission after dendritic spine formation induced by sevoflurane were associated with long-term behavioral changes. The effects of sevoflurane on mitochondrial function were also assessed to further understand the mechanism behind spinogenesis.

Methods: Postnatal day 16 to 17 mice were exposed to sevoflurane (2.5% for 2 h), and synaptic transmission was measured in the medial prefrontal cortex 6 h or 5 days later. The expression of postsynaptic proteins and mitochondrial function were measured after anesthesia. Long-term behavioral changes were assessed in adult mice.

Results: Sevoflurane increased the expression of excitatory postsynaptic proteins in male and female mice (n = 3 to 5 per group). Sevoflurane exposure in male mice transiently increased miniature excitatory postsynaptic current frequency (control: 8.53 ± 2.87; sevoflurane: 11.09 ± 2.58) but decreased miniature inhibitory postsynaptic current frequency (control: 10.18 ± 4.66; sevoflurane: 6.88 ± 2.15). Unexpectedly, sevoflurane increased miniature inhibitory postsynaptic current frequency (control: 1.81 ± 1.11; sevoflurane: 3.56 ± 1.74) in female mice (neurons, n = 10 to 21 per group). Sevoflurane also increased mitochondrial respiration in male mice (n = 5 to 8 per group). However, such changes from anesthesia during the critical period did not induce long-term behavioral consequences. Values are presented as mean ± SD.

Conclusions: Sevoflurane exposure during the critical period induces mitochondrial hyperactivity and transient imbalance of excitatory/inhibitory synaptic transmission, without long-lasting behavioral consequences. Further studies are needed to confirm sexual differences and to define the role of mitochondrial activity during anesthesia-induced spine formation.