Cited by 496Anesthesia and Neurotoxicity ResearchAnesthesia and Sedative AgentsMemory and Neural Mechanisms

Neonatal Exposure to Sevoflurane Induces Abnormal Social Behaviors and Deficits in Fear Conditioning in Mice

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Satomoto, Maiko, Satoh, Yasushi, Terui, Katsuo, Miyao, Hideki, Takishima, Kunio, Ito, Masataka, Imaki, Junko·2009·Anesthesiology

Abstract

Background: Neonatal exposure to anesthetics that block N-methyl-D-aspartate receptors and/or hyperactivate gamma-aminobutyric acid type A receptor has been shown to cause neuronal degeneration in the developing brain, leading to functional deficits later in adulthood. The authors investigated whether exposure of neonatal mice to inhaled sevoflurane causes deficits in social behavior as well as learning disabilities. Methods: Six-day-old C57BL/6 mice were exposed to 3% sevoflurane for 6 h. Activated cleaved caspase-3 immunohistochemical staining was used for detection of apoptosis. Cognitive functions were tested by pavlovian conditioned fear test. Social behavior was tested by social recognition and interaction tests. Results: Neonatal exposure to sevoflurane significantly increased the number of apoptotic cells in the brain immediately after anesthesia. It caused persistent learning deficits later in adulthood as evidenced by decreased freezing response in both contextual and cued fear conditioning. The social recognition test demonstrated that mice with neonatal exposure to sevoflurane did not develop social memory. Furthermore, these mice showed decreased interactions with a social target compared with controls in the social interaction test, indicating a social interaction deficit. The authors did not attribute these abnormalities in social behavior to impairments of general interest in novelty or olfactory sensation, because they did not detect significant differences in the test for novel inanimate object interaction or for olfaction. Conclusions: This study shows that exposure of neonatal mice to inhaled sevoflurane could cause not only learning deficits but also abnormal social behaviors resembling autism spectrum disorder.

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  1. Bittigau P, Sifringer M, Pohl D, Stadthaus D, Ishimaru M, Shimizu H, Ikeda M, Lang D, Speer A, Olney JW, Ikonomidou C: Apoptotic neurodegeneration following trauma is markedly enhanced in the immature brain. Ann Neurol 1999; 45:724-35
  2. Hussman JP: Suppressed GABAergic inhibition as a common factor in suspected etiologies of autism. Autism Dev Disord 2001; 2:247-8

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Authors
Satomoto, M., Satoh, Y., Terui, K., Miyao, H., Takishima, K., Ito, M., & Imaki, J.
Affiliations
  • National Defense Medical College (JP)
  • Assistant Professor.
  • Associate Professor, Department of Obstetric Anesthesia.
  • Saitama Medical Center, Saitama Medical University (JP)
  • Associate Professor.
  • Professor, Department of Developmental Anatomy and Regenerative Biology.
Venue
Anesthesiology
Published
2009-03-01
Volume
110
Issue
3
Pages
628-637
ISSN
0003-3022 (ISSN-L)
OpenAlex
W2036450246
Cited by
496
References
31
Citations by year
2026: 5 · 2025: 12 · 2024: 18 · 2023: 15 · 2022: 30 · 2021: 34 · 2020: 31 · 2019: 26 · 2018: 30 · 2017: 37 · 2016: 62 · 2015: 37 · 2014: 47 · 2013: 36 · 2012: 32
FWCI
7.83
Type
journal article
Language
en
Open access
Locations
  • Anesthesiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Defense Medical College
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
sevoflurane, neonatal anesthesia, inhalational anesthetics, social behavior, social recognition memory, fear conditioning, learning deficits, apoptosis, caspase-3, autism spectrum disorder, NMDA receptor antagonism, developmental neurotoxicity
MeSH terms
Sevoflurane, Animals, Animals, Newborn, Conditioning, Psychological, Fear, Learning Disabilities, Male, Memory Disorders, Methyl Ethers, Mice, Inbred C57BL, Social Behavior, Mice

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