Altered hypothalamic protein expression in a rat model of Huntington's disease.
Altered hypothalamic protein expression in a rat model of Huntington's disease.
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DOI：
10.1371/journal.pone.0047240
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Martin B
中科院分区：
文献类型：
--
作者：
Cong WN;Cai H;Wang R;Daimon CM;Maudsley S;Raber K;Canneva F;von Hörsten S;Martin B
亨廷顿舞蹈症（HD）是一种神经退行性疾病，其特征是进行性运动障碍和认知改变。能量代谢、神经内分泌功能、体重、血糖正常、食欲功能和昼夜节律也可能发生变化。这些改变的部位很可能是下丘脑。我们使用具有 51 个 CAG 重复序列的 HD 转基因 (tg) 大鼠模型来研究下丘脑功能，该模型表现出与 HD 患者相似的 HD 症状。我们进行了详细的下丘脑蛋白质组分析，并测量了症状前和症状动物中各种代谢激素和脂质的循环水平。我们的研究结果表明，HD大鼠下丘脑蛋白表达存在显着变化，例如胶质纤维酸性蛋白（GFAP）、热休克蛋白70、氧化损伤蛋白谷胱甘肽过氧化物酶（Gpx4）、糖原合成酶1（Gys1）和脂质合成酶酰基甘油-3-磷酸O-酰基转移酶1 （阿格帕特1）。此外，在出现任何运动或认知变化之前，出现症状前的动物体内各种循环代谢激素和脂质（包括胰岛素、瘦素、甘油三酯和高密度脂蛋白）均发生显着变化。这些早期代谢和脂质改变可能是下丘脑功能障碍的前驱体征。更好地了解 HD 中发生的下丘脑和代谢变化，可能会导致 HD 早期介入治疗的新疗法的开发。
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.
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