Trophic factors differentiate dopamine neurons vulnerable to Parkinson's disease

Research output: Contribution to journalArticle

Abstract

Recent studies suggest a variety of factors characterize substantia nigra neurons vulnerable to Parkinson's disease, including the transcription factors pituitary homeobox 3 (Pitx3) and orthodenticle homeobox 2 (Otx2) and the trophic factor receptor deleted in colorectal cancer (DCC), but there is limited information on their expression and localization in adult humans. Pitx3, Otx2, and DCC were immunohistochemically localized in the upper brainstem of adult humans and mice and protein expression assessed using relative intensity measures and online microarray data. Pitx3 was present and highly expressed in most dopamine neurons. Surprisingly, in our elderly subjects no Otx2 immunoreactivity was detected in dopamine neurons, although Otx2 gene expression was found in younger cases. Enhanced DCC gene expression occurred in the substantia nigra, and higher amounts of DCC protein characterized vulnerable ventral nigral dopamine neurons. Our data show that, at the age when Parkinson's disease typically occurs, there are no significant differences in the expression of transcription factors in brainstem dopamine neurons, but those most vulnerable to Parkinson's disease rely more on the trophic factor receptor DCC than other brainstem dopamine neurons. (C) 2013 Elsevier Inc. All rights reserved.

Details

Authors
  • Stefanie Reyes
  • Yuhong Fu
  • Kay L. Double
  • Veronica Cottam
  • Lachlan H. Thompson
  • Deniz Kirik
  • George Paxinos
  • Charles Watson
  • Helen M. Cooper
  • Glenda M. Halliday
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • Deleted in colorectal cancer, Dopamine neurons, Orthodenticle homeobox, 2, Pitx3, Substantia nigra
Original languageEnglish
Pages (from-to)873-886
JournalNeurobiology of Aging
Volume34
Issue number3
Publication statusPublished - 2013
Publication categoryResearch
Peer-reviewedYes