Journal
NEUROTOXICOLOGY AND TERATOLOGY
Volume 60, Issue -, Pages 69-74Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.ntt.2016.11.002
Keywords
Autism Spectrum Disorder; Shank3; Isoflurane; NR1; PSD95
Categories
Funding
- NHLBI NIH HHS [P50 HL107182] Funding Source: Medline
- NIDCR NIH HHS [K02 DE023551, R01 DE022880] Funding Source: Medline
- NIGMS NIH HHS [R01 GM120519, R01 GM049111, R01 GM110674, T32 GM075774] Funding Source: Medline
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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(+/Delta c)). These mice exhibit important characteristics of autism that mimic human autistic behavior. Our study demonstrates that a Shank3(+/Delta c) 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(+/Delta c) 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. (C) 2016 Elsevier Inc. All rights reserved.
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