title: Sevoflurane exposure during the neonatal period induces long-term memory impairment but not autism-like behaviors.
abstract: 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.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chungnam National University Hospital, Daejeon, Korea.
authors.forename: Woosuk
authors.initials: W
authors.lastname: Chung
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors.forename: Saegeun
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors.forename: Jiso
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chungnam National University Hospital, Daejeon, Korea.
authors.forename: Sangil
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chungnam National University Hospital, Daejeon, Korea.
authors.forename: Soomin
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Junyoung
authors.initials: J
authors.lastname: Heo
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors.forename: Daesoo
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chungnam National University Hospital, Daejeon, Korea.
authors.forename: Youngkwon
authors.initials: Y
authors.lastname: Ko
mesh_terms: D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001321:Autistic Disorder; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000187:drug effects; D004195:Disease Models, Animal; D057567:Memory, Long-Term / Q000187:drug effects*; D008738:Methyl Ethers / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D053148:Caspase 3
keywords: autism; long-term memory; neonatal anesthesia; neurodegeneration; sevoflurane