Altered Hypothalamic Protein Expression in a Rat Model of Huntington's Disease

  • Huntington's disease (HD) is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg) rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstraHuntington's disease (HD) is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg) rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstrate that there are significant alterations in HD rat hypothalamic protein expression such as glial fibrillary acidic protein (GFAP), heat shock protein-70, the oxidative damage protein glutathione peroxidase (Gpx4), glycogen synthase1 (Gys1) and the lipid synthesis enzyme acylglycerol-3-phosphate O-acyltransferase 1 (Agpat1). In addition, there are significant alterations in various circulating metabolic hormones and lipids in pre-symptomatic animals including, insulin, leptin, triglycerides and HDL, before any motor or cognitive alterations are apparent. These early metabolic and lipid alterations are likely prodromal signs of hypothalamic dysfunction. Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD.show moreshow less

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Metadaten
Author:Wei-na Cong, Huan Cai, Rui Wang, Caitlin M. Daimon, Stuart Maudsley, Kerstin Raber, Fabio Canneva, Stephan von Hörsten, Bronwen Martin
URN:urn:nbn:de:bvb:29-opus-37221
Document Type:Article
Language:English
Date of Publication (online):2012/10/30
Publishing Institution:Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
Release Date:2012/10/30
SWD-Keyword:-
Original publication:PLoS ONE 7.10 (2012): 30.10.2012 <http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0047240>
Institutes:Medizinische Fakultät / Medizinische Fakultät -ohne weitere Spezifikation-
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Collections:Universität Erlangen-Nürnberg / Open Access Artikel ohne Förderung / Open Access Artikel ohne Förderung 2012

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