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Trophic factors differentiate dopamine neurons vulnerable to Parkinson's disease

Reyes, Stefanie ; Fu, Yuhong ; Double, Kay L. ; Cottam, Veronica ; Thompson, Lachlan H. ; Kirik, Deniz LU ; Paxinos, George ; Watson, Charles ; Cooper, Helen M. and Halliday, Glenda M. (2013) In Neurobiology of Aging 34(3). p.873-886
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... (More)
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. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
Deleted in colorectal cancer, Dopamine neurons, Orthodenticle homeobox, 2, Pitx3, Substantia nigra
in
Neurobiology of Aging
volume
34
issue
3
pages
873 - 886
publisher
Elsevier
external identifiers
  • wos:000313117900019
  • scopus:84870514012
  • pmid:22926168
ISSN
1558-1497
DOI
10.1016/j.neurobiolaging.2012.07.019
language
English
LU publication?
yes
id
eb77110e-f4df-4e5b-88de-9a58634c06f5 (old id 3476896)
date added to LUP
2016-04-01 10:32:54
date last changed
2020-02-12 02:20:28
@article{eb77110e-f4df-4e5b-88de-9a58634c06f5,
  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.},
  author       = {Reyes, Stefanie and Fu, Yuhong and Double, Kay L. and Cottam, Veronica and Thompson, Lachlan H. and Kirik, Deniz and Paxinos, George and Watson, Charles and Cooper, Helen M. and Halliday, Glenda M.},
  issn         = {1558-1497},
  language     = {eng},
  number       = {3},
  pages        = {873--886},
  publisher    = {Elsevier},
  series       = {Neurobiology of Aging},
  title        = {Trophic factors differentiate dopamine neurons vulnerable to Parkinson's disease},
  url          = {http://dx.doi.org/10.1016/j.neurobiolaging.2012.07.019},
  doi          = {10.1016/j.neurobiolaging.2012.07.019},
  volume       = {34},
  year         = {2013},
}