目的:初步探讨β淀粉样蛋白Aβ_(25-35)损伤海马CA1区兴奋性突触的靶点及贝沙罗汀的可能拮抗效应。方法:以出生7~14 d Wistar大鼠海马脑片为研究对象,采用全细胞膜片钳技术,在电压钳模式下记录大鼠海马脑片CA1区锥体细胞自发兴奋性突触...目的:初步探讨β淀粉样蛋白Aβ_(25-35)损伤海马CA1区兴奋性突触的靶点及贝沙罗汀的可能拮抗效应。方法:以出生7~14 d Wistar大鼠海马脑片为研究对象,采用全细胞膜片钳技术,在电压钳模式下记录大鼠海马脑片CA1区锥体细胞自发兴奋性突触后电流(s EPSCs)和微小兴奋性突触后电流(mEPSCs),分析不同组神经元s EPSCs和mEPSCs幅度及频率的差异。结果:与对照组相比,经Aβ_(25-35)(1μmol/L)处理后,海马神经元sEPSCs与mEPSCs平均幅度和平均频率都显著降低(均P<0.05)。向Aβ_(25-35)处理过的海马脑片中加入贝沙罗汀(5μmol/L)后,sEPSCs与mEPSCs平均幅度和平均频率较Aβ_(25-35)组都显著提高(均P<0.05)。贝沙罗汀处理组sEPSCs与mEPSCs平均频率和平均幅度与对照组水平无显著性差异(均P>0.05)。结论:Aβ_(25-35)可作用于CA1区,导致海马锥体神经元兴奋性突触后电位降低,突触功能损伤,贝沙罗汀通过作用于突触前和突触后位点拮抗Aβ_(25-35)的损伤效应。展开更多
Radiation therapy is a standard treatment for head and neck tumors.However,patients often exhibit cognitive impairments following radiation therapy.Previous studies have revealed that hippocampal dysfunction,specifica...Radiation therapy is a standard treatment for head and neck tumors.However,patients often exhibit cognitive impairments following radiation therapy.Previous studies have revealed that hippocampal dysfunction,specifically abnormal hippocampal neurogenesis or neuroinflammation,plays a key role in radiation-induced cognitive impairment.However,the long-term effects of radiation with respect to the electrophysiological adaptation of hippocampal neurons remain poorly characterized.We found that mice exhibited cognitive impairment 3 months after undergoing 10 minutes of cranial irradiation at a dose rate of 3 Gy/min.Furthermore,we observed a remarkable reduction in spike firing and excitatory synaptic input,as well as greatly enhanced inhibitory inputs,in hippocampal CA1 pyramidal neurons.Corresponding to the electrophysiological adaptation,we found reduced expression of synaptic plasticity marker VGLUT1 and increased expression of VGAT.Furthermore,in irradiated mice,long-term potentiation in the hippocampus was weakened and GluR1 expression was inhibited.These findings suggest that radiation can impair intrinsic excitability and synaptic plasticity in hippocampal CA1 pyramidal neurons.展开更多
文摘目的:初步探讨β淀粉样蛋白Aβ_(25-35)损伤海马CA1区兴奋性突触的靶点及贝沙罗汀的可能拮抗效应。方法:以出生7~14 d Wistar大鼠海马脑片为研究对象,采用全细胞膜片钳技术,在电压钳模式下记录大鼠海马脑片CA1区锥体细胞自发兴奋性突触后电流(s EPSCs)和微小兴奋性突触后电流(mEPSCs),分析不同组神经元s EPSCs和mEPSCs幅度及频率的差异。结果:与对照组相比,经Aβ_(25-35)(1μmol/L)处理后,海马神经元sEPSCs与mEPSCs平均幅度和平均频率都显著降低(均P<0.05)。向Aβ_(25-35)处理过的海马脑片中加入贝沙罗汀(5μmol/L)后,sEPSCs与mEPSCs平均幅度和平均频率较Aβ_(25-35)组都显著提高(均P<0.05)。贝沙罗汀处理组sEPSCs与mEPSCs平均频率和平均幅度与对照组水平无显著性差异(均P>0.05)。结论:Aβ_(25-35)可作用于CA1区,导致海马锥体神经元兴奋性突触后电位降低,突触功能损伤,贝沙罗汀通过作用于突触前和突触后位点拮抗Aβ_(25-35)的损伤效应。
基金supported by the National Natural Science Foundation of China,Nos.81925031(to YT),81820108026(to YT),81972967(to WJL),81872549(to YL)the Youth Program of National Natural Science Foundation of China,No.81801229(to YTX)+3 种基金a grant from Guangdong Science and Technology Department of China,Nos.2020B1212060018(to WJL),2020B1212030004(to WJL)the Natural Science Foundation of Guangdong Province,No.2019A1515011754(to WJL)the Science and Technology Program of Guangzhou of China,No.202007030001(to YT)the Science and Technology Planning Project of Guangzhou of China,No.201704030033(to YL).
文摘Radiation therapy is a standard treatment for head and neck tumors.However,patients often exhibit cognitive impairments following radiation therapy.Previous studies have revealed that hippocampal dysfunction,specifically abnormal hippocampal neurogenesis or neuroinflammation,plays a key role in radiation-induced cognitive impairment.However,the long-term effects of radiation with respect to the electrophysiological adaptation of hippocampal neurons remain poorly characterized.We found that mice exhibited cognitive impairment 3 months after undergoing 10 minutes of cranial irradiation at a dose rate of 3 Gy/min.Furthermore,we observed a remarkable reduction in spike firing and excitatory synaptic input,as well as greatly enhanced inhibitory inputs,in hippocampal CA1 pyramidal neurons.Corresponding to the electrophysiological adaptation,we found reduced expression of synaptic plasticity marker VGLUT1 and increased expression of VGAT.Furthermore,in irradiated mice,long-term potentiation in the hippocampus was weakened and GluR1 expression was inhibited.These findings suggest that radiation can impair intrinsic excitability and synaptic plasticity in hippocampal CA1 pyramidal neurons.
