Comparative analyses of Purkinje cell gene expression profiles reveal shared molecular abnormalities in models of different polyglutamine diseases

Brain Res. 2012 Oct 24;1481:37-48. doi: 10.1016/j.brainres.2012.08.005. Epub 2012 Aug 17.


Polyglutamine (PolyQ) diseases have common features that include progressive selective neurodegeneration and the formation of protein aggregates. There is growing evidence to suggest that critical nuclear events lead to transcriptional alterations in PolyQ diseases such as spinocerebellar ataxia type 7 (SCA7) and Huntington's disease (HD), conditions which share a cerebellar degenerative phenotype. Taking advantage of laser capture microdissection technique, we compared the Purkinje cell (PC) gene expression profiles of two transgenic polyQ mouse models (HD: R6/2; SCA7: P7E) by microarray analysis that was validated by real time quantitative PCR. A large number of transcriptional alterations were detected in the R6/2 transgenic model of HD. Similar decreases in the same mRNAs, such as phospholipase C, β 3, purkinje cell protein 2 (Pcp2) and aldolase C, were found in both models. A decrease in aldolase C and phospholipase C, β 3, may lead to an increase in the vulnerability of PCs to excitotoxic events. Furthermore, downregulation of mRNAs mediated by the Pcp2-promoter is common in both models. Thus, our data reveal shared molecular abnormalities in different polyQ disorders.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ataxin-7
  • Disease Models, Animal
  • Female
  • Guanine Nucleotide Exchange Factors / genetics
  • Humans
  • Huntingtin Protein
  • Huntington Disease / genetics*
  • Huntington Disease / pathology
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics*
  • Neuropeptides / genetics
  • Oligonucleotide Array Sequence Analysis
  • Peptides / genetics*
  • Promoter Regions, Genetic / genetics
  • Purkinje Cells / pathology
  • Purkinje Cells / physiology*
  • Spinocerebellar Ataxias / genetics*
  • Spinocerebellar Ataxias / pathology
  • Transcriptome
  • Transgenes / genetics


  • ATXN7 protein, human
  • Ataxin-7
  • Atxn7 protein, mouse
  • Guanine Nucleotide Exchange Factors
  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Neuropeptides
  • Pcp2 protein, mouse
  • Peptides
  • polyglutamine