Sensitivity to isoflurane anesthesia increases in autism spectrum disorder Shank3+/c mutant mouse model

Changsheng Li, Michele Schaefer, Christy Gray, Ya Yang, Orion Furmanski, Sufang Liu, Paul F Worley, Cyrus David Mintz, Feng Tao, Roger A Johns

Research output: Contribution to journalArticle

Abstract

Autism is a heterogeneous developmental disorder characterized by impaired social interaction, impaired communication skills, and restricted and repetitive behavior. The abnormal behaviors of these patients can make their anesthetic and perioperative management difficult. Evidence in the literature suggests that some patients with autism or specific autism spectrum disorders (ASD) exhibit altered responses to pain and to anesthesia or sedation. A genetic mouse model of one particular ASD, Phelan McDermid Syndrome, has been developed that has a Shank3 haplotype truncation (Shank3 +/δc). These mice exhibit important characteristics of autism that mimic human autistic behavior. Our study demonstrates that a Shank3 +/δC mutation in mice is associated with a reduction in both the MAC and RREC50 of isoflurane and down regulation of NR1 in vestibular nuclei and PSD95 in spinal cord. Decreased expression of NR1 and PSD95 in the central nervous system of Shank3 +/δC mice could help reduce the MAC and RREC50 of isoflurane, which would warrant confirmation in a clinical study. If Shank3 mutations are found to affect anesthetic sensitivity in patients with ASD, better communication and stricter monitoring of anesthetic depth may be necessary.

Original languageEnglish (US)
JournalNeurotoxicology and Teratology
DOIs
StateAccepted/In press - Jul 3 2016

Fingerprint

Isoflurane
Anesthetics
Anesthesia
Autistic Disorder
Communication
Neurology
Vestibular Nuclei
Mutation
Genetic Models
Interpersonal Relations
Haplotypes
Spinal Cord
Down-Regulation
Central Nervous System
Monitoring
Pain
Autism Spectrum Disorder

Keywords

  • Autism Spectrum Disorder
  • Isoflurane
  • NR1
  • PSD95
  • Shank3

ASJC Scopus subject areas

  • Toxicology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

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title = "Sensitivity to isoflurane anesthesia increases in autism spectrum disorder Shank3+/c mutant mouse model",
abstract = "Autism is a heterogeneous developmental disorder characterized by impaired social interaction, impaired communication skills, and restricted and repetitive behavior. The abnormal behaviors of these patients can make their anesthetic and perioperative management difficult. Evidence in the literature suggests that some patients with autism or specific autism spectrum disorders (ASD) exhibit altered responses to pain and to anesthesia or sedation. A genetic mouse model of one particular ASD, Phelan McDermid Syndrome, has been developed that has a Shank3 haplotype truncation (Shank3 +/δc). These mice exhibit important characteristics of autism that mimic human autistic behavior. Our study demonstrates that a Shank3 +/δC mutation in mice is associated with a reduction in both the MAC and RREC50 of isoflurane and down regulation of NR1 in vestibular nuclei and PSD95 in spinal cord. Decreased expression of NR1 and PSD95 in the central nervous system of Shank3 +/δC mice could help reduce the MAC and RREC50 of isoflurane, which would warrant confirmation in a clinical study. If Shank3 mutations are found to affect anesthetic sensitivity in patients with ASD, better communication and stricter monitoring of anesthetic depth may be necessary.",
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AU - Schaefer, Michele

AU - Gray, Christy

AU - Yang, Ya

AU - Furmanski, Orion

AU - Liu, Sufang

AU - Worley, Paul F

AU - Mintz, Cyrus David

AU - Tao, Feng

AU - Johns, Roger A

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