Anxiolytic effect of CPEB1 knockdown on the amygdala of a mouse model of inflammatory pain

Brain Res Bull. 2018 Mar:137:156-165. doi: 10.1016/j.brainresbull.2017.12.002. Epub 2017 Dec 11.

Abstract

Anxiety disorders are a category of mental disorders characterized by feelings of anxiety, stress, and fear attached to various sources. However, their pathogenesis is complicated and has not been fully elucidated. The amygdala is a vital brain region that regulates anxiety and mental disorders. Cytoplasmic polyadenylation element binding protein 1 (CPEB1) mediates the extension of the mRNA polyadenylation tail and facilitates the translation of target RNA. CPEB1 is closely related to neuronal diseases, such as Fragile X Syndrome, learning and memory disorders, and chronic pain. In this study, the role of CPEB1 in anxiety development was determined in a pain-mediated anxiety mouse model. The anxiety model was established in mice by injecting with Complete Freund's Adjuvant (CFA) into the hindpaw. CFA injection then led to anxiety-like behaviors and increased the CPEB1 levels in the mouse basolateral amygdala (BLA). CPEB1 enhancement facilitated the translation of GluA1, GluN2A, GluN2B, PSD95, and GABA receptors, which disturbed the E/I balance in the BLA as shown by enhanced excitatory presynaptic release and reduced inhibitory presynaptic release. CPEB1 knockdown with AAV-CPEB1-shRNA alleviated the anxiety-like behaviors but not the pain-like behaviors by enhancing inhibitory transmission in the BLA of model mice. The data suggest that CPEB1 participates in anxiety development by regulating excitatory/inhibitory synaptic transmission in the BLA.

Keywords: Amygdala; Anxiety; CFA; CPEB1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / metabolism*
  • Basolateral Nuclear Complex / metabolism*
  • Cells, Cultured
  • Disease Models, Animal
  • Disks Large Homolog 4 Protein / metabolism
  • Freund's Adjuvant
  • Gene Knockdown Techniques
  • Genetic Vectors
  • Hindlimb
  • Inflammation / metabolism*
  • Inflammation / psychology
  • Male
  • Mice, Inbred C57BL
  • Neural Inhibition / physiology
  • Neurons / metabolism
  • Pain / metabolism*
  • Pain / psychology
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Receptors, AMPA / metabolism
  • Receptors, GABA / metabolism
  • Synaptic Transmission / physiology
  • Transcription Factors / deficiency*
  • Transcription Factors / genetics
  • mRNA Cleavage and Polyadenylation Factors / deficiency*
  • mRNA Cleavage and Polyadenylation Factors / genetics

Substances

  • Cpeb1 protein, mouse
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • RNA, Small Interfering
  • Receptors, AMPA
  • Receptors, GABA
  • Transcription Factors
  • mRNA Cleavage and Polyadenylation Factors
  • Freund's Adjuvant