Molecular Mechanism for Stress-Induced Depression Assessed by Sequencing miRNA and mRNA in Medial Prefrontal Cortex

PLoS One. 2016 Jul 18;11(7):e0159093. doi: 10.1371/journal.pone.0159093. eCollection 2016.

Abstract

Background: Major depression is a prevalent mood disorder. Chronic stress is presumably main etiology that leads to the neuron and synapse atrophies in the limbic system. However, the intermediate molecules from stresses to neuronal atrophy remain elusive, which we have studied in the medial prefrontal cortices from depression mice.

Methods and results: The mice were treated by the chronic unpredictable mild stress (CUMS) until they expressed depression-like behaviors confirmed by the tests of sucrose preference, forced swimming and Y-maze. High-throughput sequencings of microRNA and mRNA in the medial prefrontal cortices were performed in CUMS-induced depression mice versus control mice to demonstrate the molecular profiles of major depression. In the medial prefrontal cortices of depression-like mice, the levels of mRNAs that translated the proteins for the GABAergic synapses, dopaminergic synapses, myelination, synaptic vesicle cycle and neuronal growth were downregulated. miRNAs of regulating these mRNAs are upregulated.

Conclusion: The deteriorations of GABAergic and dopaminergic synapses as well as axonal growth are associated with CUMS-induced depression.

MeSH terms

  • Animals
  • Depressive Disorder, Major / etiology*
  • Depressive Disorder, Major / genetics*
  • Depressive Disorder, Major / pathology
  • Disease Models, Animal
  • Gene Expression Regulation*
  • Gene Regulatory Networks
  • Male
  • Mice, Inbred C57BL
  • MicroRNAs / analysis
  • MicroRNAs / genetics*
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / pathology*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics*
  • Stress, Psychological / complications*
  • Stress, Psychological / genetics
  • Stress, Psychological / pathology

Substances

  • MicroRNAs
  • RNA, Messenger

Grants and funding

This study is granted by the National Basic Research Program (2013CB531304) and Natural Science Foundation China (81471123) to JHW.