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

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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

DOI 10.1097/aln.0b013e3181974fa2

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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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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.
ORCID: Satomoto, Maiko
Satoh, Yasushi
Miyao, Hideki
Ito, Masataka
Venue: Anesthesiology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2009-03-01
Volume: 110
Issue: 3
Pages: 628-637
ISSN: 0003-3022 (ISSN-L)
DOI: 10.1097/aln.0b013e3181974fa2
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: bronze
doi.org
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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Neonatal Exposure to Sevoflurane Induces Abnormal Social Behaviors and Deficits in Fear Conditioning in Mice

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