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Sevoflurane exposure during the neonatal period induces long‐term memory impairment but not autism‐like behaviors
Author(s) -
Chung Woosuk,
Park Saegeun,
Hong Jiso,
Park Sangil,
Lee Soomin,
Heo Junyoung,
Kim Daesoo,
Ko Youngkwon
Publication year - 2015
Publication title -
pediatric anesthesia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.704
H-Index - 82
eISSN - 1460-9592
pISSN - 1155-5645
DOI - 10.1111/pan.12694
Subject(s) - sevoflurane , autism , medicine , open field , neurotoxicity , autism spectrum disorder , neurodevelopmental disorder , elevated plus maze , anesthesia , anxiety , neuroscience , psychiatry , psychology , toxicity
Summary Objective To examine whether neonatal exposure to sevoflurane induces autism‐like behaviors in mice. Background There are continuing reports regarding the potential negative effects of anesthesia on the developing brain. Recently, several studies suggest that neurotoxicity caused by anesthesia may lead to neurodevelopmental impairments. However, unlike reports focusing on learning and memory, there are only a few animal studies focusing on neurodevelopmental disorders after general anesthesia. Therefore, we have focused on autism, a representative neurodevelopmental disorder. Methods Neonatal mice (P6–7) were exposed to a titrated dose of sevoflurane for 6 h. Apoptosis was evaluated by assessing the expression level of cleaved (activated) caspase‐3. Autism‐like behaviors, general activity, anxiety level, and long‐term memory were evaluated with multiple behavioral assays. Results Western blotting confirmed that neonatal exposure to sevoflurane increased the expression level of activated caspase‐3, indicative of apoptosis. Mice exposed to sevoflurane also showed impaired long‐term memory in fear tests. However, sevoflurane‐exposed mice did not exhibit autism‐like features in all of the following assays: social interaction (three‐chamber test, caged social interaction), social communication (ultrasonic vocalization test), or repetitive behavior (self‐grooming test, digging). There were also no differences in general activity (open field test, home cage activity) and anxiety (open field test, light‐dark box) after sevoflurane exposure. Conclusions Our results confirm previous studies that neonatal sevoflurane exposure causes neurodegeneration and long‐term memory impairment in mice. However, sevoflurane did not induce autism‐like features. Our study suggests that mice are more vulnerable to long‐term memory deficits than autism‐like behaviors after exposure to sevoflurane.