title: Altered hypothalamic protein expression in a rat model of Huntington's disease.
abstract: 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.
authors.affiliation: Metabolism Unit, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America.
authors.forename: Wei-na
authors.initials: WN
authors.lastname: Cong
authors.forename: Huan
authors.initials: H
authors.lastname: Cai
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Daimon
authors.forename: Stuart
authors.initials: S
authors.lastname: Maudsley
authors.forename: Kerstin
authors.initials: K
authors.lastname: Raber
authors.forename: Fabio
authors.initials: F
authors.lastname: Canneva
authors.forename: Stephan
authors.initials: S
authors.lastname: von Hörsten
authors.forename: Bronwen
authors.initials: B
authors.lastname: Martin
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006006:Glycogen Synthase / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007031:Hypothalamus / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D051381:Rats; D055647:Rats, Transgenic; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D018840:HSP70 Heat-Shock Proteins; C499524:Htt protein, rat; D000071058:Huntingtin Protein; D007328:Insulin; D020738:Leptin; D008075:Lipoproteins, HDL; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014280:Triglycerides; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; C523860:glutathione peroxidase 4, rat; D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D006006:Glycogen Synthase