Genipin normalizes depression-like behavior induced by prenatal stress through inhibiting DNMT1

Epigenetics. 2018;13(3):310-317. doi: 10.1080/15592294.2018.1450033. Epub 2018 May 3.

Abstract

Synthetic antidepressants in current use for the complex etiopathogeneses of depression have slow response and remission as well as various unpleasant side effects. As a result, it is imperative to develop new antidepressants with more effectiveness and less severe side effects. Recent studies demonstrated that genipin, the aglycon of geniposide, extracted from Gardenia jasminoides Ellis has antidepressive effects. However, knowledge regarding the molecular mechanisms of its antidepressant effects remains limited. Employing a depression-like mouse model, we confirmed that genipin is capable of correcting depressions-like behaviors induced by prenatal stress in offspring from prenatally stressed dams (defined as PRS mice). In further experiments, we found that the effect of genipin on PRS mice occurs through DNA demethylation by inhibiting DNA methyltransferase 1 (DNMT1), normalizing the expression of reduced brain-derived neurotrophic factor (BDNF) in the hippocampus.

Keywords: BDNF; DNA methylation; DNMT1; Genipin; depression; mouse; prenatal stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / administration & dosage
  • Brain-Derived Neurotrophic Factor / genetics*
  • DNA (Cytosine-5-)-Methyltransferase 1 / genetics*
  • DNA Methylation / drug effects
  • DNA Methylation / genetics*
  • Depression / drug therapy*
  • Depression / genetics
  • Depression / pathology
  • Disease Models, Animal
  • Female
  • Gardenia / chemistry
  • Gene Expression Regulation / drug effects
  • Hippocampus / drug effects
  • Humans
  • Iridoids / administration & dosage*
  • Iridoids / chemistry
  • Mice
  • Pregnancy
  • Prenatal Exposure Delayed Effects / drug therapy
  • Prenatal Exposure Delayed Effects / genetics
  • Prenatal Exposure Delayed Effects / pathology
  • Stress, Psychological / drug therapy
  • Stress, Psychological / genetics
  • Stress, Psychological / pathology

Substances

  • Antidepressive Agents
  • Bdnf protein, mouse
  • Brain-Derived Neurotrophic Factor
  • Iridoids
  • genipin
  • DNA (Cytosine-5-)-Methyltransferase 1
  • Dnmt1 protein, mouse

Grants and funding

This work is supported by National Natural Science Foundation of China [grant number NSFC 81271264].