Transglutaminase 2 Induces Deficits in Social Behavior in Mice. Academic Article uri icon

Overview

abstract

  • Impairments in social behavior are highly implicated in many neuropsychiatric disorders. Recent studies indicate a role for endoplasmic reticulum (ER) stress in altering social behavior, but the underlying mechanism is not known. In the present study, we examined the role of transglutaminase 2 (TG2), a calcium-dependent enzyme known to be induced following ER stress, in social behavior in mice. ER stress induced by tunicamycin administration increased TG2 protein levels in the mouse prefrontal cortex (PFC). PFC-specific inhibition of TG2 attenuated ER stress-induced deficits in social behavior. Conversely, overexpression of TG2 in the PFC resulted in social behavior impairments in mice. In addition, systemic administration of cysteamine, a TG2 inhibitor, attenuated social behavior deficits. Our preliminary findings using postmortem human brain samples found increases in TG2 mRNA and protein levels in the middle frontal gyrus of subjects with autism spectrum disorder. These findings in mice and human postmortem brain samples identify changes in TG2 activity in the possible dysregulation of social behavior.

publication date

  • December 13, 2018

Research

keywords

  • Autism Spectrum Disorder
  • Behavior, Animal
  • Endoplasmic Reticulum Stress
  • GTP-Binding Proteins
  • Prefrontal Cortex
  • Social Behavior
  • Transglutaminases

Identity

PubMed Central ID

  • PMC6311865

Scopus Document Identifier

  • 85060036586

Digital Object Identifier (DOI)

  • 10.1155/2018/2019091

PubMed ID

  • 30647729

Additional Document Info

volume

  • 2018