Abnormal hippocampal BDNF and miR-16 expression is associated with depression-like behaviors induced by stress during early life

PLoS One. 2012;7(10):e46921. doi: 10.1371/journal.pone.0046921. Epub 2012 Oct 8.

Abstract

Some environmental stressors lead to the onset of depression via inhibiting hippocampal BDNF expression, but other environmental stressors-induced depression exhibits no change in BDNF expression. The underlying mechanisms behind the divergence remain unknown. In this study, depression-like behaviors were induced in rats by maternal deprivation (MD) and chronic unpredictable stress (CUPS). Depression-like behaviors were tested by open field test, forced swimming test, and sucrose consumption test. BDNF and miR-16 expressions in the hippocampus were examined by real-time PCR. MD and CUPS rats crawled less distance, exhibited decreased vertical activity, and produced more fecal pellets than control rats in the open field test. However, MD rats crawled less distance and produced significantly less fecal pellets than CUPS rats. In the forced swimming and sucrose consumption tests, CUPS and MD rats exhibited longer floating time and consumed less sucrose than control rats, but MD rats exhibited shorter floating time and consumed less sucrose than CUPS rats. MD but not CUPS rats showed lower BDNF mRNA and higher miR-16 expression than control rats. In MD rats, BDNF mRNA expression negatively correlated with the expression of miR-16. BDNF expression positively correlated with the total distance rats crawled and vertical activity in the open field test while miR-16 expression negatively correlated the two behaviors. BDNF positively correlated with sucrose preference rate while miR-16 negatively correlated with sucrose preference rate of the sucrose consumption test. Our study suggests that MD and CUPS induced different depression-like behaviors in rats. Depression induced by MD but not CUPS was significantly associated with upregulation of miR-16 and possibly subsequent downregulation of BDNF in hippocampus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal*
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Depression / genetics
  • Depression / metabolism*
  • Depression / psychology
  • Female
  • Gene Expression Regulation*
  • Hippocampus / metabolism*
  • Maternal Deprivation
  • MicroRNAs / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Psychological / complications*
  • Time Factors

Substances

  • Brain-Derived Neurotrophic Factor
  • MIRN16 microRNA, rat
  • MicroRNAs
  • RNA, Messenger

Grants and funding

This work was supported by National Natural Science Foundation of China (No. 81071097). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.