Upregulation of spinal ASIC1 by miR-485 mediates enterodynia in adult offspring rats with prenatal maternal stress

CNS Neurosci Ther. 2021 Feb;27(2):244-255. doi: 10.1111/cns.13542. Epub 2020 Dec 13.

Abstract

Aims: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disease characterized by abdominal pain. Our recent study has shown that the acid-sensitive ion channel 1 (ASIC1) in dorsal root ganglion (DRG) is involved in stomachache of adult offspring rats subjected with prenatal maternal stress (PMS). MiR-485 is predicted to target the expression of ASIC1. The aim of the present study was designed to determine whether miR-485/ASIC1 signaling participates in enterodynia in the spinal dorsal horn of adult offspring rats with PMS.

Methods: Enterodynia was measured by colorectal distension (CRD). Western blotting, qPCR, and in situ hybridization were performed to detect the expression of ASICs and related miRNAs. Spinal synaptic transmission was also recorded by patch clamping.

Results: PMS offspring rats showed that spinal ASIC1 protein expression and synaptic transmission were significantly enhanced. Administration of ASICs antagonist amiloride suppressed the synaptic transmission and enterodynia. Besides, PMS induced a significant reduction in the expression of miR-485. Upregulating the expression markedly attenuated enterodynia, reversed the increase in ASIC1 protein and synaptic transmission. Furthermore, ASIC1 and miR-485 were co-expressed in NeuN-positive spinal dorsal horn neurons.

Conclusions: Overall, these data suggested that miR-485 participated in enterodynia in PMS offspring, which is likely mediated by the enhanced ASIC1 activities.

Keywords: acid-sensitive ion channel 1; enterodynia; miR-485; prenatal maternal stress; spinal dorsal horn.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Pain / etiology
  • Abdominal Pain / genetics
  • Abdominal Pain / metabolism*
  • Acid Sensing Ion Channels / biosynthesis*
  • Acid Sensing Ion Channels / genetics
  • Age Factors
  • Animals
  • Female
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Pregnancy
  • Prenatal Exposure Delayed Effects / genetics
  • Prenatal Exposure Delayed Effects / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / metabolism*
  • Stress, Psychological / complications
  • Stress, Psychological / genetics
  • Stress, Psychological / metabolism*
  • Up-Regulation / physiology

Substances

  • Acid Sensing Ion Channels
  • Asic1 protein, rat
  • MIRN485 microRNA, rat
  • MicroRNAs