Proteomics- and transcriptomics-based screening of differentially expressed proteins and genes in brain of Wig rat: a model for attention deficit hyperactivity disorder (ADHD) research

J Proteome Res. 2008 Jun;7(6):2471-89. doi: 10.1021/pr800025t. Epub 2008 May 6.

Abstract

Two global omics approaches were applied to develop an inventory of differentially expressed proteins and genes in Wig rat, a promising animal model of attention-deficit hyperactivity disorder (ADHD). The frontal cortex, striatum, and midbrain of Wig rat at 4 weeks of age were dissected for proteomics and transcriptomics analyses. Two-dimensional gel electrophoresis detected 13, 1, and 16 differentially expressed silver nitrate-stained spots in the frontal cortex, striatum, and midbrain, respectively. Peptide mass fingerprinting/tandem mass spectrometry identified 19 nonredundant proteins, belonging to 7 functional categories, namely, signal transduction, energy metabolism, cellular transport, protein with binding function, protein synthesis, cytoskeleton, and cell rescue. Interestingly, 10 proteins that were indentified in the present study were also previously reported in studies involving neurodegenerative diseases and psychiatric disorders, such as Alzheimer's disease (AD), Parkinson's disease, and Schizophrenia. Moreover, some of the proteins identified in the midbrain were involved in synaptic vesicular transport, suggesting abnormality in neurotransmitter release in this region. On the other hand, transcriptomics analysis of combined frontal cortex, striatum, and midbrain by rat whole genome 44K DNA oligo microarray revealed highly up-regulated (28) and down-regulated (33) genes. Functional categorization of these genes showed cellular transport, metabolism, protein fate, signal transduction, and transcription as the major categories, with 26% genes of unknown function. Some of the identified genes were related to AD, fragile X syndrome, and ADHD. This is a first comprehensive study providing insight into molecular components in Wig rat brain, and will help to elucidate the roles of identified proteins and genes in Wig rat brain, hopefully leading to uncovering the pathogenesis of ADHD.

MeSH terms

  • Animals
  • Attention Deficit Disorder with Hyperactivity / genetics
  • Attention Deficit Disorder with Hyperactivity / metabolism
  • Attention Deficit Disorder with Hyperactivity / pathology
  • Basal Ganglia / metabolism
  • Brain / metabolism*
  • Disease Models, Animal
  • Electrophoresis, Gel, Two-Dimensional
  • Frontal Lobe / metabolism
  • Gene Expression Profiling / methods*
  • Male
  • Mesencephalon / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Proteins / genetics*
  • Proteins / metabolism*
  • Proteomics / methods*
  • Rats
  • Rats, Inbred LEC
  • Rats, Mutant Strains
  • Rats, Wistar
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Tandem Mass Spectrometry

Substances

  • Proteins