Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 60, 69-74

Sensitivity to Isoflurane Anesthesia Increases in Autism Spectrum Disorder Shank3 +/∆c Mutant Mouse Model

Affiliations

Sensitivity to Isoflurane Anesthesia Increases in Autism Spectrum Disorder Shank3 +/∆c Mutant Mouse Model

Changsheng Li et al. Neurotoxicol Teratol.

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.

Keywords: Autism Spectrum Disorder; Isoflurane; NR1; PSD95; Shank3.

Figures

Fig. 1
Fig. 1. Shank3+/ΔC mice have no functional motor impairment
Performance on the rotarod test was not significantly different between the Shank3+/ΔC mice and WT mice. Data are shown as mean ± SD. (n=10/group, P=0.54).
Fig. 2
Fig. 2. Expression of proteins in Shank3 signaling pathway in caudal brain of WT and Shank3+/ΔC mice
A: Representative Western blot showing expression of shank3 in caudal brain. Expression of β-actin was used as an internal reference. B: Quantification of band density shows that Shank3 expression was significantly lower in Shank3+/ΔC mice than in WT mice.*P<0.01; n=6/group. C: Representative Western blot showing expression of NR1, NR2A/B, PSD95, GKAP, Homer1b/c, mGluR1, and mGluR5 incaudal brain. D: Quantification of band densities shows that only NR1 expression was down regulated in the caudal brain of Shank3+/ΔC mice compared to that in WT mice.*P<0.01; n=6/group.
Fig. 3
Fig. 3. Expression of proteins in Shank3 signaling pathway in spinal cord of WT and Shank3+/ΔC mice
A: Representative Western blot showing expression of Shank3 in spinal cord. Expression of β-actin was used as an internal reference. B: Quantification of band density shows that Shank3 expression was significantly lower in Shank3+/ΔC mice than in WT mice.*P<0.01;n=6/group. C: Representative Western blot showing expression of NR1, NR2A/B, PSD95, GKAP, Homer1b/c, mGluR1, and mGluR5 in spinal cord. D: Quantification of band densities shows that only PSD95 expression was down regulated in the spinal cord of Shank3+/ΔC mice compared to that in WT mice.*P<0.01;n=6/group.

Similar articles

See all similar articles

Cited by 2 PubMed Central articles

MeSH terms

Feedback