Abnormal Hippocampal BDNF and miR-16 Expression Is Associated with Depression-Like Behaviors Induced by Stress during Early Life

Mei Bai,Shuqiao Yao,Sheng Zhang,Li Zhang,Yi Zhang,Xiuwu Zhang,Jinyao Yi,Xiongzhao Zhu,Liang Xue,Judith Homberg

doi:10.1371/journal.pone.0046921

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.

Highlights

Depression is a highly complicated psychiatric disorder that can greatly damage the social functions of the sufferers
Chronic unpredictable stress and maternal deprivation paradigms are commonly used to simulate the effect of adverse experiences in adulthood or early life of a person, respectively
maternal deprivation (MD) induced less total distance crawled in the open field test and sucrose preference rate in sucrose consumption test than chronic unpredictable stress (CUPS)

Summary

Introduction

Depression is a highly complicated psychiatric disorder that can greatly damage the social functions of the sufferers. This disorder has become a major burden for our society [1]. Raising the monoamine level in synaptic clefts has been a major strategy for treating depression during the past 50 years. Evidence from animal experiments and postmortem studies has consistently suggested that reduced BDNF level in the hippocampus is responsible for decreased proliferation of hippocampal neurons and consequent onset of depression [4,5,6,7]. Environmental stressors could induce depressive performances by affecting hippocampal BDNF level [5,7,8,9]. The underlying mechanisms by which environmental stressors regulate BDNF expression remain unidentified

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Results

Conclusion