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Thyroid stimulating hormone - receptor overexpression in brain of patients with down syndrome and Alzheimer's disease

机译:唐氏综合症和阿尔茨海默氏病患者的大脑中促甲状腺激素受体过表达

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Thyroid hormone abnormalities are strongly associated with Down Syndrome (DS) with elevated thyroid stimulating hormone (TSH) levels as the most consistent finding. Using subtractive hybridization for gene hunting we found significant overexpression of mRNA levels for the TSH - receptor (TSH-R) in brain of a fetus with DS. Based upon this observation we determined TSH-R protein levels in five brain regions of patients with DS(n = 8), Alzheimer disease(AD, n = 8) and controls (C, n = 8). Western blots revealed significantly elevated immunoreactive TSH-R protein(s) 40 kD and 61 kD in temporal and frontal cortex of patients with DS and, unexpectedly, in AD. Levels for the 40 kD protein in temporal cortex were 1.00 +- 0.036 (arbitrary units +- SD) IN c, 1.35 +- 0.143 in DS, 1.52 +- 0.128 in AD; in frontal cortex: 1.00 +- 0.046 in C, 1.10 +- 0.03 in DS, 1.10 +- 0.038 in AD. Levels for the 61 kD protein in temporal cortex were 1.01 +- 0.015 in C, 1.47 +- 0.013 in DS, 1.623 +- 0.026 in AD; in frontal cortex: 1.02 +- 0.020 in C, 1.18 +- 0.123 in DS, 1.48 +- 0.020 in AD. These results show that elevated brain immunoreactive TSH-R is not specific for DS and maybe reflecting apoptosis, a hallmark of both neurodegenerative disorders, as it is well-documented that the thyroid hormone system is involved in the control of programmed cell death.
机译:甲状腺激素异常与唐氏综合症(DS)密切相关,甲状腺刺激激素(TSH)水平升高是最一致的发现。使用消减杂交进行基因狩猎,我们发现DS胎儿大脑中TSH-受体(TSH-R)的mRNA水平明显过表达。基于此观察,我们确定了DS(n = 8),阿尔茨海默病(AD,n = 8)和对照(C,n = 8)患者的五个大脑区域中的TSH-R蛋白水平。 Western印迹显示,DS患者的颞叶和额叶皮质中,以及AD中出乎意料的,免疫反应性TSH-R蛋白的含量分别为40 kD和61 kD。颞皮层中40 kD蛋白的水平为1.00 +-0.036(任意单位+-SD)IN c,DS中1.35±0.143,AD 1.52±0.128;在额叶皮层中:C时1.00±0.046,DS中1.10±0.03,AD中1.10±0.038。颞皮质中61 kD蛋白的水平在C中为1.01 +-0.015,在DS中为1.47 +-0.013,在AD中为1.623 +-0.026;在额叶皮层中:C中为1.02±0.020,DS中为1.18±0.123,AD中为1.48±0.020。这些结果表明,脑免疫反应性TSH-R升高对DS不是特异性的,并且可能反映了凋亡,这是两种神经退行性疾病的标志,因为有充分的文献证明甲状腺激素系统参与了程序性细胞死亡的控制。

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