Skip Navigation



Human Molecular Genetics Advance Access published online on September 19, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl394
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
15/21/3177    most recent
ddl394v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Nguyen, H. P.
Right arrow Articles by von Hörsten, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nguyen, H. P.
Right arrow Articles by von Hörsten, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press. All rights reserved
Received July 5, 2006
Revised August 30, 2006
Accepted September 12, 2006

Article

Behavioral abnormalities precede neuropathological markers in rats transgenic for Huntington's Disease

Huu Phuc Nguyen 1, Philipp Kobbe 2, Henning Rahne 2, Till Wörpel 2, Burkard Jäger 3, Michael Stephan 2, Reinhard Pabst 2, Carsten Holzmann 4, Olaf Riess 5, Hubert Korr 6, Orsolya Kántor 6, Elisabeth Petrasch-Parwez 7, Ronald Wetzel 8, Alexander Osmand 8, and Stephan von Hörsten 9 *

1 Department of Functional and Applied Anatomy, Medical School of Hannover, Germany; Department of Medical Genetics, University of Tübingen, Germany
2 Department of Functional and Applied Anatomy, Medical School of Hannover, Germany
3 Department of Psychosomatics and Psychotherapy, Medical School of Hannover, Germany
4 Department of Medical Genetics, University of Rostock, Germany
5 Department of Medical Genetics, University of Tübingen, Germany
6 Department of Anatomy and Cell Biology, RWTH Aachen University, Germany
7 Department of Neuroanatomy and Molecular Brain Research, University of Bochum, Germany
8 Department of Medicine, University of Tennessee, Knoxville, TN, USA
9 Department of Functional and Applied Anatomy, Medical School of Hannover, Germany; Experimental Therapy, Franz-Penzoldt-Center, Friedrich-Alexander-University of Erlangen-Nürnberg, Germany

* To whom correspondence should be addressed.
Stephan von Hörsten, E-mail: Stephan.v.Hoersten{at}ze.uni-erlangen.de


  Abstract

Huntington's disease (HD) is caused by an expanded CAG repeat leading to the synthesis of an aberrant protein and to the formation of polyglutamine (polyQ)-containing inclusions and aggregates. Limited information is available concerning the association of neuropathological markers with the development of behavioral markers in HD. Using a previously generated transgenic rat model of HD (tgHD rat), we performed association studies on the time course of behavioral symptoms (motor function, learning, anxiety) and the appearance of striatal atrophy, 1C2 immunopositive aggregates, and polyQ recruitment sites, a precursor to these aggregates. At the age of 1 month, tgHD rats exhibited reduced anxiety and improved motor performance, while at 6 months motor impairments and at 9 months cognitive decline occurred. In contrast, polyQ recruitment sites appeared at around 6 to 9 months of age, indicating that HD-like behavioral markers preceded the appearance of currently detectable neuropathological markers. Interestingly, numerous punctate sites containing polyQ aggregates were also seen in areas receiving afferents from the densely recruiting regions suggesting either transport of recruitment-competent aggregates to terminal projections where initially 1C2 positive aggregates were formed or different internal properties of neurons in different regions. Furthermore, striatal atrophy was observed at the age of 12 months. Taken together, our findings support the hypothesis of a dynamic process leading to region and age-specific polyQ recruitment and aggregation. The dissociation of onset between behavioral and neuropathological markers is suggestive of as yet undetected processes, which contribute to the early phenotype of these HD transgenic rats.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
F. J. Bode, M. Stephan, H. Suhling, R. Pabst, R. H. Straub, K. A. Raber, M. Bonin, H. P. Nguyen, O. Riess, A. Bauer, et al.
Sex differences in a transgenic rat model of Huntington's disease: decreased 17{beta}-estradiol levels correlate with reduced numbers of DARPP32+ neurons in males
Hum. Mol. Genet., September 1, 2008; 17(17): 2595 - 2609.
[Abstract] [Full Text] [PDF]

Home page
 Proc R Soc BHome page
K. Littin, A. Acevedo, W. Browne, J. Edgar, M. Mendl, D. Owen, C. Sherwin, H. Wurbel, and C. Nicol
Towards humane end points: behavioural changes precede clinical signs of disease in a Huntington's disease model
Proc R Soc B, August 22, 2008; 275(1645): 1865 - 1874.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.