Deficiency of SHANK3 isoforms impairs thermal hyperalgesia and dysregulates the expression of postsynaptic proteins in the spinal cord.

Neuroscience Research
Min HuangTao Xu

Abstract

SHANK3 is one of the scaffolding proteins in the postsynaptic density (PSD). Pain perception and underlying mechanisms were investigated in Shank3 exon 21 deficient (Shank3△C) mice. Sixty-six mice were attributed according to their genotype to three groups: (1) wild-type (WT), (2) heterozygous Shank3△C/+, and (3) homozygous Shank3△C/△C. Complete Freund's adjuvant (CFA) was used to induce inflammatory pain, and thermal hyperalgesia was determined. CFA treatment reduced the thermal threshold in the WT group; groups expressing mutations of Shank3 (△C/+ and △C/△C) had higher thresholds after CFA administration compared to the WT group. Mice with Shank3 mutations (△C/+ or △C/△C) had a lower expression of GluN2A and IP3R proteins and a higher expression of mGluR5 protein in the PSD compared to WT mice without changes in GluN1, GluN2B, and Homer expression. The crosslinking of Homer-IP3R, but not Homer-mGluR5, was decreased in the total lysate. Deficit of Shank3 exon 21 may lead to impaired perception of thermal pain in mice under inflammatory conditions. This impairment may result from protein dysregulation in the PSD like downregulation of the GluN2A subunit, which may reduce NMDAR-mediated currents, and/or decreased crosslinking be...Continue Reading

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