Effect of chronic mild stress and imipramine on the proteome of the rat dentate gyrus

J Neurochem. 2010 May;113(4):848-59. doi: 10.1111/j.1471-4159.2010.06652.x. Epub 2010 Feb 23.

Abstract

The present study uses a proteomic approach to examine possible alterations of protein expression in the hippocampus of rats that are subjected to chronic mild stress (CMS). These rats serve as an animal model that was developed to mimic anhedonia, which is one of the core symptoms of depression. As antidepressant treatment is effective after a few weeks of administration, we also aimed to identify changes that were linked to chronic (once daily for 4 weeks) and 'pulse' (once a week) administration of imipramine. Fifteen differential proteins were identified with 2D electrophoresis followed by mass spectrometry. Although both methods of imipramine administration restored normal sucrose consumption in rats that were subjected to CMS, the molecular mechanisms of these two therapies were different. CMS-induced changes in the levels of dynactin 2, Ash 2, non-neuronal SNAP25 and alpha-enolase were reversed by chronic imipramine, but 'pulse' treatment was not that effective.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents, Tricyclic / pharmacology
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Appetite / drug effects
  • Appetite / physiology
  • Chronic Disease
  • DNA-Binding Proteins / drug effects
  • DNA-Binding Proteins / metabolism
  • Dentate Gyrus / metabolism*
  • Dentate Gyrus / physiopathology
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / etiology
  • Depressive Disorder / metabolism*
  • Disease Models, Animal
  • Dynactin Complex
  • Electrophoresis, Gel, Two-Dimensional
  • Feeding Behavior / drug effects
  • Feeding Behavior / physiology
  • Imipramine / pharmacology*
  • Imipramine / therapeutic use
  • Male
  • Mass Spectrometry
  • Microtubule-Associated Proteins / drug effects
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / drug effects
  • Nerve Tissue Proteins / metabolism
  • Nuclear Proteins / drug effects
  • Nuclear Proteins / metabolism
  • Phosphopyruvate Hydratase / drug effects
  • Phosphopyruvate Hydratase / metabolism
  • Proteome / drug effects
  • Proteome / metabolism*
  • Rats
  • Rats, Wistar
  • Stress, Psychological / complications
  • Stress, Psychological / metabolism*
  • Stress, Psychological / physiopathology
  • Synaptosomal-Associated Protein 25 / drug effects
  • Synaptosomal-Associated Protein 25 / metabolism
  • Transcription Factors / drug effects
  • Transcription Factors / metabolism

Substances

  • Antidepressive Agents, Tricyclic
  • Ash2l protein, mouse
  • DNA-Binding Proteins
  • Dctn2 protein, mouse
  • Dynactin Complex
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Proteome
  • Snap25 protein, rat
  • Synaptosomal-Associated Protein 25
  • Transcription Factors
  • Phosphopyruvate Hydratase
  • Imipramine