Dendrite ramification affects synaptic strength and plays a crucial role in memory. Previous studies revealed a correlation between beta 2-adrenergic receptor dysfunction and Alzheimer＇s disease （AD）, although the ...Dendrite ramification affects synaptic strength and plays a crucial role in memory. Previous studies revealed a correlation between beta 2-adrenergic receptor dysfunction and Alzheimer＇s disease （AD）, although the mechanism involved is still poorly understood. The current study investigated the potential effect of the selective β2-adrenergic receptor antagonist, ICI 118551 （ICI）, on Aβ deposits and AD-related cognitive impairment. Morris water maze test results demonstrated that the performance of AD-transgenic （TG） mice treated with ICI （AD-TG/ICI） was significantly poorer compared with NaCl-treated AD-TG mice （AD-TG/NaCl）, suggesting that β2-adrenergic receptor blockage by ICI might reduce the learning and memory abilities of mice. Golgi staining and immunohistochemical staining revealed that blockage of the β2-adrenergic receptor by ICI treatment decreased the number of dendritic branches, and ICI treatment in AD-TG mice decreased the expression of hippocampal synaptophysin and synapsin 1. Western blot assay results showed that the blockage of β2-adrener- gic receptor increased amyloid-β accumulation by downregulating hippocampal a-secretase activity and increasing the phosphorylation of amyloid precursor protein. These findings suggest that blocking the β2-adrenergic receptor inhibits dendrite ramification of hippocampal neurons in a mouse model of AD.展开更多
目的探讨老年心力衰竭(心衰)模型大鼠心脏及肺β3肾上腺素能受体(β3-AR)变化及相互关系。方法选择雄性老年Wistar大鼠48只,应用主动脉结扎术制备心衰模型。大鼠随机分为假手术组和心衰组,每组24只,每组术后5、7、9、11周每个时间点各6...目的探讨老年心力衰竭(心衰)模型大鼠心脏及肺β3肾上腺素能受体(β3-AR)变化及相互关系。方法选择雄性老年Wistar大鼠48只,应用主动脉结扎术制备心衰模型。大鼠随机分为假手术组和心衰组,每组24只,每组术后5、7、9、11周每个时间点各6只。测定2组大鼠血流动力学、病理、心肌及肺组织β3-AR mRNA表达。结果与假手术组比较,心衰组术后9、11周心率、左心室收缩末压、左心室压力最大上升速率显著降低,左心室压力最大下降速率显著增高,5、7、9、11周左心室舒张末压显著增高,差异有统计学意义(P<0.01)。心衰组术后7周出现肺水肿,术后9周出现心肌核坏死。心衰组术后5、7、9、11周每个时间点肺组织β3-AR mRNA表达较2周前均明显减低(P<0.05)。心衰组术后9、11周心肌组织β3-AR mRNA表达较假手术组明显升高(1.21±0.26 vs 0.98±0.22,1.26±0.23 vs 1.05±0.24,P<0.01)。结论心衰时,肺组织β3-AR mRNA表达下降,心肌组织表达升高,且肺的变化先于心肌组织。展开更多
Objective To explore the effects of thyroid hormone (TH) on cardiac function and peripheral lymphocyte β-adrenoceptors (β-ARs) of patients with chronic congestive heart failure (CHF).Methods Twenty-eight patients wi...Objective To explore the effects of thyroid hormone (TH) on cardiac function and peripheral lymphocyte β-adrenoceptors (β-ARs) of patients with chronic congestive heart failure (CHF).Methods Twenty-eight patients with class III or IV advanced CHF due to dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM) were randomly divided into groups A and B. L-thyroxine (L-T50) was administered to group B. Exercise tolerance, chest X-rays, and echocardiographic parameters were obtained before and after one month of treatment, Ficoll-hypaque solution was used to separate peripheral lymphocytes, and 125l-pindolol radioligand binding was used to measure β-AR levels in peripheral lymphocytes.Results L-T50 therapy improved cardiac output [CO, (2. 98±0. 31 )L/min vs (3. 24 ±0. 28) L/min, P<0. 01], left ventricular ejection fraction (LVEF, 26.21%±3.21% vs 37.93% ±9.01%, P< 0. 01), and decreased isovolumetric relaxation time (IVRT, 0.12 ±0. 04 vs 0.10 ±0. 02, P<0. 01). Serum TH levels and the maximal number of β-AR binding sites (βmax) in peripheral lymphocytes were lower in patients with CHF than in normal healthy people, but L-T50 administration induced a β-AR up-regulation on peripheral lymphocyte surfaces. L-T50 was well tolerated without episodes of ischemia or arrhythmia. There was no significant change in heart rate or metabolic rate.Conclusion TH administration improves cardiac function and β-AR expression in peripheral lymphocytes of patients with CHF.展开更多
基金supported by the Key Laboratory of Brain Disease Bioinformation of Jiangsu Province of China,No.Jsbl1202
文摘Dendrite ramification affects synaptic strength and plays a crucial role in memory. Previous studies revealed a correlation between beta 2-adrenergic receptor dysfunction and Alzheimer＇s disease （AD）, although the mechanism involved is still poorly understood. The current study investigated the potential effect of the selective β2-adrenergic receptor antagonist, ICI 118551 （ICI）, on Aβ deposits and AD-related cognitive impairment. Morris water maze test results demonstrated that the performance of AD-transgenic （TG） mice treated with ICI （AD-TG/ICI） was significantly poorer compared with NaCl-treated AD-TG mice （AD-TG/NaCl）, suggesting that β2-adrenergic receptor blockage by ICI might reduce the learning and memory abilities of mice. Golgi staining and immunohistochemical staining revealed that blockage of the β2-adrenergic receptor by ICI treatment decreased the number of dendritic branches, and ICI treatment in AD-TG mice decreased the expression of hippocampal synaptophysin and synapsin 1. Western blot assay results showed that the blockage of β2-adrener- gic receptor increased amyloid-β accumulation by downregulating hippocampal a-secretase activity and increasing the phosphorylation of amyloid precursor protein. These findings suggest that blocking the β2-adrenergic receptor inhibits dendrite ramification of hippocampal neurons in a mouse model of AD.
文摘目的探讨老年心力衰竭(心衰)模型大鼠心脏及肺β3肾上腺素能受体(β3-AR)变化及相互关系。方法选择雄性老年Wistar大鼠48只,应用主动脉结扎术制备心衰模型。大鼠随机分为假手术组和心衰组,每组24只,每组术后5、7、9、11周每个时间点各6只。测定2组大鼠血流动力学、病理、心肌及肺组织β3-AR mRNA表达。结果与假手术组比较,心衰组术后9、11周心率、左心室收缩末压、左心室压力最大上升速率显著降低,左心室压力最大下降速率显著增高,5、7、9、11周左心室舒张末压显著增高,差异有统计学意义(P<0.01)。心衰组术后7周出现肺水肿,术后9周出现心肌核坏死。心衰组术后5、7、9、11周每个时间点肺组织β3-AR mRNA表达较2周前均明显减低(P<0.05)。心衰组术后9、11周心肌组织β3-AR mRNA表达较假手术组明显升高(1.21±0.26 vs 0.98±0.22,1.26±0.23 vs 1.05±0.24,P<0.01)。结论心衰时,肺组织β3-AR mRNA表达下降,心肌组织表达升高,且肺的变化先于心肌组织。
基金the Zhengzhou Railway Bureau Science Fund, China (99w33).
文摘Objective To explore the effects of thyroid hormone (TH) on cardiac function and peripheral lymphocyte β-adrenoceptors (β-ARs) of patients with chronic congestive heart failure (CHF).Methods Twenty-eight patients with class III or IV advanced CHF due to dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM) were randomly divided into groups A and B. L-thyroxine (L-T50) was administered to group B. Exercise tolerance, chest X-rays, and echocardiographic parameters were obtained before and after one month of treatment, Ficoll-hypaque solution was used to separate peripheral lymphocytes, and 125l-pindolol radioligand binding was used to measure β-AR levels in peripheral lymphocytes.Results L-T50 therapy improved cardiac output [CO, (2. 98±0. 31 )L/min vs (3. 24 ±0. 28) L/min, P<0. 01], left ventricular ejection fraction (LVEF, 26.21%±3.21% vs 37.93% ±9.01%, P< 0. 01), and decreased isovolumetric relaxation time (IVRT, 0.12 ±0. 04 vs 0.10 ±0. 02, P<0. 01). Serum TH levels and the maximal number of β-AR binding sites (βmax) in peripheral lymphocytes were lower in patients with CHF than in normal healthy people, but L-T50 administration induced a β-AR up-regulation on peripheral lymphocyte surfaces. L-T50 was well tolerated without episodes of ischemia or arrhythmia. There was no significant change in heart rate or metabolic rate.Conclusion TH administration improves cardiac function and β-AR expression in peripheral lymphocytes of patients with CHF.
