title: Sensitivity to isoflurane anesthesia increases in autism spectrum disorder Shank3+/∆cmutant 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+/ΔCmutation 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+/ΔCmice 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.
authors.affiliation: Department of Anesthesiology, Affiliated Anti-cancer Hospital of Zhengzhou University, Zhengzhou, Henan Province 450008, China; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Schaefer
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Christy
authors.initials: C
authors.lastname: Gray
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Ya
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Orion
authors.initials: O
authors.lastname: Furmanski
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Basic Medical School of Zhengzhou University, Zhengzhou, Henan Province 450001, China.
authors.forename: Sufang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Worley
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: C David
authors.initials: CD
authors.lastname: Mintz
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Anesthesiology and Critical Care Medicine, Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, TX 75246, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Tao
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: rajohns@jhmi.edu.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Johns
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000235:genetics / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008840:Microfilament Proteins; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis; D057897:Reflex, Righting / Q000187:drug effects; D045442:Rotarod Performance Test; D013116:Spinal Cord / Q000378:metabolism; D014726:Vestibular Nuclei / Q000378:metabolism
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; C121673:Gprin1 protein, mouse; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C492356:Shank3 protein, mouse; D007530:Isoflurane
keywords: Autism Spectrum Disorder; Isoflurane; NR1; PSD95; Shank3