目的探讨S14G-Humanin(HNG)对β-淀粉样蛋白(Aβ)致海马CA1区突触长时程增强(LTP)抑制的影响。方法制备小鼠海马脑片(n=20),分为4组:正常对照组、400 n M Aβ25-35组、400 n M Aβ25-35+200 n M HNG组、400 n M Aβ25-35+400 n M HNG组...目的探讨S14G-Humanin(HNG)对β-淀粉样蛋白(Aβ)致海马CA1区突触长时程增强(LTP)抑制的影响。方法制备小鼠海马脑片(n=20),分为4组:正常对照组、400 n M Aβ25-35组、400 n M Aβ25-35+200 n M HNG组、400 n M Aβ25-35+400 n M HNG组。应用多通道细胞外记录系统(MED系统)记录各组海马脑片兴奋性突触后电位(EPSP)的斜率,并与基础对照的EPSP斜率相比,计算相应的百分比作为LTP数值,观察可溶性Aβ25-35对海马CA1区LTP的抑制作用以及不同浓度HNG对Aβ25-35致LTP抑制效应的影响。结果 400 n M Aβ25-35组LTP值较正常对照组显著减少[(102.5±2.0)%vs(148.1±8.0)%,P<0.01],表明其可显著抑制海马CA1区LTP的产生;400 n M Aβ25-35+200 n M HNG组较400 n M Aβ25-35组LTP值显著增加[(121.3±2.9)%vs(102.5±2.0)%,P<0.01],表明其可部分减少400 n M Aβ25-35对海马CA1区LTP的抑制效应;而400 n M Aβ25-35+400 n M HNG组较400 n M Aβ25-35组LTP显著增加[(143.0±4.3)%vs(102.5±2.0)%,P<0.01],并与正常对照组相比无统计学差异[(143.0±4.3)%vs(148.1±8.0)%,P>0.05],表明其可以完全逆转400 n M Aβ25-35对海马CA1区LTP的抑制效应。结论 HNG能够逆转可溶性Aβ25-35对海马CA1区LTP的抑制作用,提示HNG对Aβ所致的突触可塑性损害具有神经保护作用。展开更多
Humanin is a potential therapeutic agent for Alzheimer’s disease, and its derivative, S14G-humanin, is 1 000-fold stronger in its neuroprotective effect against Alzheimer’s disease-relevant insults. Alt-hough effect...Humanin is a potential therapeutic agent for Alzheimer’s disease, and its derivative, S14G-humanin, is 1 000-fold stronger in its neuroprotective effect against Alzheimer’s disease-relevant insults. Alt-hough effective, the detailed molecular mechanism through which S14G-humanin exerts its effects remains unclear. Data from this study showed that fibril ar amyloid-beta 40 disturbed cel ular ho-meostasis through the cel membrane, increasing intracel ular calcium, generating reactive oxygen species, and decreasing the mitochondrial membrane potential. S14G-humanin restored these re-sponses. The results suggested that S14G-humanin blocked the effects of amyloid-beta 40 on the neuronal cel membrane, and restored the disturbed cel ular homeostasis, thereby exerting a neuroprotective effect on hippocampal neurons.展开更多
文摘目的探讨S14G-Humanin(HNG)对β-淀粉样蛋白(Aβ)致海马CA1区突触长时程增强(LTP)抑制的影响。方法制备小鼠海马脑片(n=20),分为4组:正常对照组、400 n M Aβ25-35组、400 n M Aβ25-35+200 n M HNG组、400 n M Aβ25-35+400 n M HNG组。应用多通道细胞外记录系统(MED系统)记录各组海马脑片兴奋性突触后电位(EPSP)的斜率,并与基础对照的EPSP斜率相比,计算相应的百分比作为LTP数值,观察可溶性Aβ25-35对海马CA1区LTP的抑制作用以及不同浓度HNG对Aβ25-35致LTP抑制效应的影响。结果 400 n M Aβ25-35组LTP值较正常对照组显著减少[(102.5±2.0)%vs(148.1±8.0)%,P<0.01],表明其可显著抑制海马CA1区LTP的产生;400 n M Aβ25-35+200 n M HNG组较400 n M Aβ25-35组LTP值显著增加[(121.3±2.9)%vs(102.5±2.0)%,P<0.01],表明其可部分减少400 n M Aβ25-35对海马CA1区LTP的抑制效应;而400 n M Aβ25-35+400 n M HNG组较400 n M Aβ25-35组LTP显著增加[(143.0±4.3)%vs(102.5±2.0)%,P<0.01],并与正常对照组相比无统计学差异[(143.0±4.3)%vs(148.1±8.0)%,P>0.05],表明其可以完全逆转400 n M Aβ25-35对海马CA1区LTP的抑制效应。结论 HNG能够逆转可溶性Aβ25-35对海马CA1区LTP的抑制作用,提示HNG对Aβ所致的突触可塑性损害具有神经保护作用。
基金supported by grants from Henan Medical Technologies R&D Program in China,No.200703023,201203130Henan Key Science and Technology Project in China,No.112102310684
文摘Humanin is a potential therapeutic agent for Alzheimer’s disease, and its derivative, S14G-humanin, is 1 000-fold stronger in its neuroprotective effect against Alzheimer’s disease-relevant insults. Alt-hough effective, the detailed molecular mechanism through which S14G-humanin exerts its effects remains unclear. Data from this study showed that fibril ar amyloid-beta 40 disturbed cel ular ho-meostasis through the cel membrane, increasing intracel ular calcium, generating reactive oxygen species, and decreasing the mitochondrial membrane potential. S14G-humanin restored these re-sponses. The results suggested that S14G-humanin blocked the effects of amyloid-beta 40 on the neuronal cel membrane, and restored the disturbed cel ular homeostasis, thereby exerting a neuroprotective effect on hippocampal neurons.
