Alteration in the expression of exon IIC transcripts of brain-derived neurotrophic factor gene by simvastatin [correction of simvastain] in chronic mild stress in mice: a possible link with dopaminergic pathway

Can J Physiol Pharmacol. 2014 Dec;92(12):985-92. doi: 10.1139/cjpp-2014-0125. Epub 2014 Oct 16.

Abstract

We have investigated the influence of dopaminergic agents on the expression of brain-derived neurotrophic factor (BDNF) gene in relation with lipid levels in chronic mild stress (CMS). Mice subjected to CMS were treated with simvastatin (10 mg/kg, per os (orally)) along with bromocriptine (2 mg/kg, intraperitoneally (ip)), levodopa (200 mg/kg, ip), or haloperidol (0.1 mg/kg, ip) for 14 days. CMS produced a decrease in sucrose intake and an increase in serum cholesterol and triglycerides levels with a decrease in high-density lipoprotein cholesterol, which were prevented by simvastatin. This was greater when it was combined with bromocriptine or levodopa. Haloperidol significantly prevented the simvastatin-induced increase in sucrose intake but not the alterations in lipids. There was an upregulation in the expression of BDNF exon-IIA and -IIB transcripts by CMS but not the exon-IIC transcripts. Simvastatin could increase expression of exon-IIC transcripts in stressed mice. This was partially increased by bromocriptine. Haloperidol significantly prevented simvastatin-induced increase in expression of BDNF exon-IIC transcripts. The results showed a positive correlation between expression of BDNF exon-IIC transcripts and sucrose intake. In conclusion, our data suggest the involvement of lipid levels and BDNF exon-IIC transcripts in CMS-induced behaviour in mice, possibly through the dopaminergic system.

Keywords: BDNF exon II transcripts; cholesterol; cholestérol; depression; dopamine; dépression; statines; statins; transcrits de l’exon-II du BDNF.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Bromocriptine / pharmacology
  • Chronic Disease
  • Dopamine / metabolism*
  • Dopamine Agents / pharmacology
  • Eating / drug effects
  • Exons
  • Haloperidol / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Levodopa / pharmacology
  • Lipid Metabolism / drug effects
  • Male
  • Mice
  • Signal Transduction
  • Simvastatin / pharmacology*
  • Stress, Psychological / drug therapy
  • Stress, Psychological / metabolism*
  • Sucrose / administration & dosage
  • Transcription, Genetic

Substances

  • Brain-Derived Neurotrophic Factor
  • Dopamine Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Bromocriptine
  • Levodopa
  • Sucrose
  • Simvastatin
  • Haloperidol
  • Dopamine