Comparative proteome analysis of thalamus in MK-801-treated rats

Research output: Contribution to journalArticle

Abstract

Two-dimensional gel-electrophoresis in combination with mass spectrometry is a powerful approach to compare protein expression in brain tissues. Using this proteomic approach, and based on the hypothesis that schizophrenia involves hypoglutamergic brain function, alterations in protein levels in the thalamus of rats treated with the N-methyl-D-aspartate (NMDA) receptor antagonist [+]-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]-cycloheptene-5,10-iminehydrogenmaleate (MK-801), as compared to saline-treated animals, were assessed in an unbiased fashion. The rats were divided into two groups; group 1 (short-term treated) and group 2 (long-term treated). In group 1, the levels of seven proteins were increased and four proteins reduced. In group 2, the levels of six proteins were reduced. Several of the altered proteins (heat shock proteins 60 and 72, albumin, dihydropyrimidinase related protein-2, aldolase c, and malate dehydrogenase) have previously been connected to schizophrenia. Alterations of other proteins (dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex E2, guanine deaminase, alpha-enolase, aconitase, ATP-synthase and alpha-internexin), have not, to the best of our knowledge, earlier been implicated in schizophrenia pathology. Our results show the high potential of using proteomic methods for the validation of animal models of schizophrenia and to identify new proteins involved in the pathophysiological mechanisms of schizophrenia.

Details

Authors
  • Linda Paulson
  • Peter Martin
  • Carol L Nilsson
  • Elisabeth Ljung
  • Ann Westman-Brinkmalm
  • Kaj Blennow
  • Pia Davidsson
External organisations
  • University of Gothenburg
Research areas and keywords

Keywords

  • Animals, Dizocilpine Maleate, Electrophoresis, Gel, Two-Dimensional, Excitatory Amino Acid Antagonists, Mass Spectrometry, N-Methylaspartate, Proteome, Proteomics, Rats, Rats, Sprague-Dawley, Sodium Chloride, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Thalamus, Journal Article, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)819-25
Number of pages7
JournalProteomics
Volume4
Issue number3
Publication statusPublished - 2004 Mar
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes