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...

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Autores principales:	Wei-na Cong, Huan Cai, Rui Wang, Caitlin M Daimon, Stuart Maudsley, Kerstin Raber, Fabio Canneva, Stephan von Hörsten, Bronwen Martin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/17a865b49aac4ad5a0751487a9b7e5a9
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spelling	oai:doaj.org-article:17a865b49aac4ad5a0751487a9b7e5a92021-11-18T08:11:34ZAltered hypothalamic protein expression in a rat model of Huntington's disease.1932-620310.1371/journal.pone.0047240https://doaj.org/article/17a865b49aac4ad5a0751487a9b7e5a92012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23094041/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Huntington'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.Wei-na CongHuan CaiRui WangCaitlin M DaimonStuart MaudsleyKerstin RaberFabio CannevaStephan von HörstenBronwen MartinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e47240 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wei-na Cong Huan Cai Rui Wang Caitlin M Daimon Stuart Maudsley Kerstin Raber Fabio Canneva Stephan von Hörsten Bronwen Martin Altered hypothalamic protein expression in a rat model of Huntington's disease.
description	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 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.
format	article
author	Wei-na Cong Huan Cai Rui Wang Caitlin M Daimon Stuart Maudsley Kerstin Raber Fabio Canneva Stephan von Hörsten Bronwen Martin
author_facet	Wei-na Cong Huan Cai Rui Wang Caitlin M Daimon Stuart Maudsley Kerstin Raber Fabio Canneva Stephan von Hörsten Bronwen Martin
author_sort	Wei-na Cong
title	Altered hypothalamic protein expression in a rat model of Huntington's disease.
title_short	Altered hypothalamic protein expression in a rat model of Huntington's disease.
title_full	Altered hypothalamic protein expression in a rat model of Huntington's disease.
title_fullStr	Altered hypothalamic protein expression in a rat model of Huntington's disease.
title_full_unstemmed	Altered hypothalamic protein expression in a rat model of Huntington's disease.
title_sort	altered hypothalamic protein expression in a rat model of huntington's disease.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/17a865b49aac4ad5a0751487a9b7e5a9
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Altered hypothalamic protein expression in a rat model of Huntington's disease.

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