[目的]观察茸菖胶囊对月经性癫痫神经元模型的N-甲基-D-天冬氨酸(NMDA)受体的影响,探讨其作用机制。[方法]以外源性添加雌二醇(E2)的无镁诱导的癫痫神经元(月经性癫痫神经元模型)为研究对象,随机分为7组:对照组、癫痫模型组、月经性癫...[目的]观察茸菖胶囊对月经性癫痫神经元模型的N-甲基-D-天冬氨酸(NMDA)受体的影响,探讨其作用机制。[方法]以外源性添加雌二醇(E2)的无镁诱导的癫痫神经元(月经性癫痫神经元模型)为研究对象,随机分为7组:对照组、癫痫模型组、月经性癫痫模型组、丙戊酸钠组、茸菖低剂量组、茸菖中剂量组和茸菖高剂量组。观察各组神经元形态、放电频率、静息膜电位、24 h NMDA电流变化、NMDA受体1(NR1)、NMDA受体2A(NR2A)蛋白表达情况。[结果]与对照组相比,月经性癫痫模型组高频高幅棘波放电明显增多、神经元数目明显减少,放电频率明显增加、静息膜电位明显升高、24 h NMDA通道电流密度明显增加(P<0.05或P<0.01),NR1蛋白表达明显降低、NR2A蛋白表达明显升高(P<0.05或P<0.01)。与月经性癫痫模型组相比,丙戊酸钠组高频高幅棘波放电减少、神经元数目增多,放电频率明显减少(P<0.05),静息膜电位未见明显降低、24 h NMDA通道电流密度未见明显降低(P>0.05),NR1、NR2A蛋白表达未见明显改变(P>0.05);茸菖高剂量组高频高幅棘波放电明显减少、神经元数目明显增多,放电频率明显减少、静息膜电位明显降低、24 h NMDA通道电流密度明显降低(P<0.05),NR2A蛋白表达明显降低(P<0.05),NR1蛋白表达未见明显升高(P>0.05)。[结论]茸菖胶囊可能通过下调NR2A蛋白表达,降低NMDA受体介导的神经的异常兴奋,从而减轻外源性添加E2的无镁癫痫神经元的异常放电,发挥抗癫痫作用。展开更多
目的观察恩氟烷、异氟烷的遗忘作用与NMDA受体的关系。方法小鼠分别腹腔注射恩氟烷(0.4ml.kg-1)或异氟烷(0.3ml.kg-1)建立遗忘模型,在跳台实验和避暗实验中分别观察不同剂量NMDA(25、50、75ng)侧脑室注射(intracerebroventricular injec...目的观察恩氟烷、异氟烷的遗忘作用与NMDA受体的关系。方法小鼠分别腹腔注射恩氟烷(0.4ml.kg-1)或异氟烷(0.3ml.kg-1)建立遗忘模型,在跳台实验和避暗实验中分别观察不同剂量NMDA(25、50、75ng)侧脑室注射(intracerebroventricular injection,icv)对遗忘小鼠错误次数(error times,ETs)、跳台潜伏期(step down latency,SDL)、步入潜伏期(step through latency,STL)的影响。结果侧脑室注射NMDA(50、75ng)可减少恩氟烷、异氟烷所致遗忘小鼠的ETs,延长SDL和STL。结论侧脑室注射NMDA可部分改善恩氟烷、异氟烷的遗忘作用,NMDA受体是二者所致遗忘作用的重要靶位。展开更多
N-methyl-D-aspartate receptors(NMDARs)play crucial roles in neuronal plasticity and brain function by sensing key neurotransmitters,such as glutamate and glycine.In a tour-de-force,Zhang et al.[1]provide the first ima...N-methyl-D-aspartate receptors(NMDARs)play crucial roles in neuronal plasticity and brain function by sensing key neurotransmitters,such as glutamate and glycine.In a tour-de-force,Zhang et al.[1]provide the first images of native NMDARs directly extracted from rat brains,revealing key aspects of NMDAR assembly and diversity.展开更多
Growth arrest DNA damage-inducible protein 45β(GADD45B)has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related ps...Growth arrest DNA damage-inducible protein 45β(GADD45B)has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes.However,its precise role and mechanism of action in stress susceptibility remain elusive.In this study,we found a significant reduction in GADD45B expression specifically in the ventral,but not the dorsal hippocampal CA1(dCA1)of stress-susceptible mice.Furthermore,we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation(LTP)in the ventral hippocampal CA1(vCA1).Importantly,through pharmacological inhibition using the NMDA receptor antagonist MK801,we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP.Collectively,these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.展开更多
文摘[目的]观察茸菖胶囊对月经性癫痫神经元模型的N-甲基-D-天冬氨酸(NMDA)受体的影响,探讨其作用机制。[方法]以外源性添加雌二醇(E2)的无镁诱导的癫痫神经元(月经性癫痫神经元模型)为研究对象,随机分为7组:对照组、癫痫模型组、月经性癫痫模型组、丙戊酸钠组、茸菖低剂量组、茸菖中剂量组和茸菖高剂量组。观察各组神经元形态、放电频率、静息膜电位、24 h NMDA电流变化、NMDA受体1(NR1)、NMDA受体2A(NR2A)蛋白表达情况。[结果]与对照组相比,月经性癫痫模型组高频高幅棘波放电明显增多、神经元数目明显减少,放电频率明显增加、静息膜电位明显升高、24 h NMDA通道电流密度明显增加(P<0.05或P<0.01),NR1蛋白表达明显降低、NR2A蛋白表达明显升高(P<0.05或P<0.01)。与月经性癫痫模型组相比,丙戊酸钠组高频高幅棘波放电减少、神经元数目增多,放电频率明显减少(P<0.05),静息膜电位未见明显降低、24 h NMDA通道电流密度未见明显降低(P>0.05),NR1、NR2A蛋白表达未见明显改变(P>0.05);茸菖高剂量组高频高幅棘波放电明显减少、神经元数目明显增多,放电频率明显减少、静息膜电位明显降低、24 h NMDA通道电流密度明显降低(P<0.05),NR2A蛋白表达明显降低(P<0.05),NR1蛋白表达未见明显升高(P>0.05)。[结论]茸菖胶囊可能通过下调NR2A蛋白表达,降低NMDA受体介导的神经的异常兴奋,从而减轻外源性添加E2的无镁癫痫神经元的异常放电,发挥抗癫痫作用。
文摘目的观察恩氟烷、异氟烷的遗忘作用与NMDA受体的关系。方法小鼠分别腹腔注射恩氟烷(0.4ml.kg-1)或异氟烷(0.3ml.kg-1)建立遗忘模型,在跳台实验和避暗实验中分别观察不同剂量NMDA(25、50、75ng)侧脑室注射(intracerebroventricular injection,icv)对遗忘小鼠错误次数(error times,ETs)、跳台潜伏期(step down latency,SDL)、步入潜伏期(step through latency,STL)的影响。结果侧脑室注射NMDA(50、75ng)可减少恩氟烷、异氟烷所致遗忘小鼠的ETs,延长SDL和STL。结论侧脑室注射NMDA可部分改善恩氟烷、异氟烷的遗忘作用,NMDA受体是二者所致遗忘作用的重要靶位。
文摘N-methyl-D-aspartate receptors(NMDARs)play crucial roles in neuronal plasticity and brain function by sensing key neurotransmitters,such as glutamate and glycine.In a tour-de-force,Zhang et al.[1]provide the first images of native NMDARs directly extracted from rat brains,revealing key aspects of NMDAR assembly and diversity.
基金supported by the National Natural Science Foundation of China(82201667,82371195,and 82304474)the Research Fund of Jianghan University(2023JCYJ15).
文摘Growth arrest DNA damage-inducible protein 45β(GADD45B)has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes.However,its precise role and mechanism of action in stress susceptibility remain elusive.In this study,we found a significant reduction in GADD45B expression specifically in the ventral,but not the dorsal hippocampal CA1(dCA1)of stress-susceptible mice.Furthermore,we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation(LTP)in the ventral hippocampal CA1(vCA1).Importantly,through pharmacological inhibition using the NMDA receptor antagonist MK801,we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP.Collectively,these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
