Early adolescent stress-induced changes in prefrontal cortex miRNA-135a and hippocampal miRNA-16 in male rats

Dev Psychobiol. 2017 Dec;59(8):958-969. doi: 10.1002/dev.21558. Epub 2017 Sep 25.

Abstract

Early-life stress increases susceptibility to post-traumatic stress disorders (PTSD), in which the dysfunction of 5-hydroxytryptamine plays an important role. miRNA-135a in the prefrontal cortex (PFC) and miRNA-16 in the hippocampus (HIP) are closely related to the 5-HT neurotransmitter system. Here, we investigated behavior, miRNA-135a in the PFC, miRNA-16 in the HIP, and 5-HT1AR expression in both brain regions in adolescent and adult rats that were exposed to inescapable stress during their adolescence. Paroxetine hydrochloride and corticotropin-releasing factor antagonist (CP-154,526) were used as intervening measures. Our study demonstrated that early adolescent stress induced anxiety-like behaviors and spatial memory damage, a reduction in miRNA-135a expression was associated with increased 5-HT1AR expression in PFC, and increased miRNA-16 expression in the HIP of stressed rats. Drug treatments alleviated behaviors and reversed the miRNA-135a, miRNA-16, and 5-HT1AR expression in stressed rats.

Keywords: 5-HT1A receptor; miRNA-135a; miRNA-16; post-traumatic stress disorder; vulnerability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Anxiety / drug therapy
  • Anxiety / etiology
  • Anxiety / metabolism*
  • Disease Models, Animal
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Male
  • MicroRNAs / drug effects
  • MicroRNAs / metabolism*
  • Paroxetine / pharmacology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism*
  • Pyrimidines / pharmacology
  • Pyrroles / pharmacology
  • Rats
  • Receptor, Serotonin, 5-HT1A / drug effects
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Spatial Memory / drug effects
  • Spatial Memory / physiology*
  • Stress, Psychological / complications
  • Stress, Psychological / metabolism*
  • Stress, Psychological / physiopathology*

Substances

  • CP 154526
  • MIRN135 microRNA, rat
  • MIRN16 microRNA, rat
  • MicroRNAs
  • Pyrimidines
  • Pyrroles
  • Receptors, Corticotropin-Releasing Hormone
  • Serotonin Uptake Inhibitors
  • Receptor, Serotonin, 5-HT1A
  • Paroxetine