Evidence for Dysfunction of the Nigrostriatal Pathway in the R6/1 Line of Transgenic Huntington's Disease Mice.

Research output: Contribution to journalArticle


The present multidisciplinary study examined nigrostriatal dopamine and striatal amino acid transmission in the R6/1 line of transgenic Huntington's disease (HD) mice expressing exon 1 of the HD gene with 115 CAG repeats. Although the number of tyrosine hydroxylase-positive neurons was not reduced and nigrostriatal connectivity remained intact in 16-week-old R6/1 mice, the size of tyrosine hydroxylase-positive neurons in the substantia nigra was reduced by 15%, and approximately 30% of these cells exhibited aggregated huntingtin. In addition, using in vivo microdialysis, we found that basal extracellular striatal dopamine levels were reduced by 70% in R6/1 mice compared to their wild-type littermates. Intrastriatal perfusion with malonate in R6/1 mice resulted in a short-lasting, attenuated increase in local dopamine release compared to wild-type mice. Furthermore, the size of the malonate-induced striatal lesion was 80% smaller in these animals. Taken together, these findings suggest that a functional deficit in nigrostriatal dopamine transmission may contribute to the behavioral phenotype and the resistance to malonate-induced neurotoxicity characteristic of R6/1 HD mice.


  • Åsa Petersén
  • Zoe Puschban
  • Julie Lotharius
  • B NicNiocaill
  • P Wiekop
  • W T O'Connor
  • Patrik Brundin
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences


  • Huntington's disease, malonate, microdialysis, substantia nigra, striatum, dopamine
Original languageEnglish
Pages (from-to)134-146
JournalNeurobiology of Disease
Issue number1
Publication statusPublished - 2002
Publication categoryResearch