Effects of CPEB1 in the anterior cingulate cortex on visceral pain in mice

Brain Res. 2019 Jun 1:1712:55-62. doi: 10.1016/j.brainres.2019.02.001. Epub 2019 Feb 4.

Abstract

Patients with irritable bowel syndrome suffer from chronic visceral pain, and in some of them, this is accompanied by anxiety comorbidity. Cytoplasmic polyadenylation element binding protein 1 (CPEB1) mediates the cytoplasmic polyadenylation of mRNAs and facilitates their translation. Our previous studies have shown that CPEB1 knockdown in the amygdala exerts anxiolytic but not analgesic effects in a mouse model of inflammatory pain. However, the roles of CPEB1 in the anterior cingulate cortex (ACC) in visceral pain modulation remain unclear. In this study, a visceral pain mouse model was established by injecting zymosan into the colon of mice. Zymosan injection significantly induced visceral pain- and anxiety-like behaviors in mice and increased the levels of GluA1, phosphorylated GluA1 at S845 and S831, and CPEB1 in the ACC. CPEB1 knockdown in the ACC by AAV-CPEB1-shRNA reduced zymosan-induced pain- and anxiety-like behaviors in mice. This observation was closely correlated with reduced AMPA receptor, synaptophysin, and PSD95 levels. These data suggest that CPEB1 in the ACC is a potential therapeutic target for visceral pain and anxiety comorbidity.

Keywords: ACC; Anxiety; CPEB1; Visceral pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / metabolism
  • Disease Models, Animal
  • Gyrus Cinguli / metabolism*
  • Gyrus Cinguli / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / metabolism
  • Receptors, AMPA / metabolism
  • Synaptophysin / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Visceral Pain / metabolism*
  • Visceral Pain / physiopathology
  • Zymosan / pharmacology
  • mRNA Cleavage and Polyadenylation Factors / genetics
  • mRNA Cleavage and Polyadenylation Factors / metabolism*

Substances

  • Cpeb1 protein, mouse
  • RNA, Messenger
  • Receptors, AMPA
  • Synaptophysin
  • Transcription Factors
  • mRNA Cleavage and Polyadenylation Factors
  • Zymosan
  • glutamate receptor ionotropic, AMPA 1