学习和记忆是大脑对外界有关信息获取、处理、存储和提取的过程,其所依赖的生物学基础是神经元之间通过突触相互连接形成复杂的神经网络,启动一系列生化级联反应,导致突触可塑性变化,如长时程增强（long term potential,LTP）和长时程...学习和记忆是大脑对外界有关信息获取、处理、存储和提取的过程,其所依赖的生物学基础是神经元之间通过突触相互连接形成复杂的神经网络,启动一系列生化级联反应,导致突触可塑性变化,如长时程增强（long term potential,LTP）和长时程抑制（long term depression,LTD）,其中,LTP与学习记忆的关系尤为密切。展开更多
Objective To characterize the function of a new xanomeline-derived M 1 agonist, 3-[3-（3-florophenyl-2-propyn- 1- ylthio）-1,2,5-thiadiazol-4-yl]-1,2,5,6- tetrahydro-1-methylpyridine Oxalate （EUK1001）, the acute tox...Objective To characterize the function of a new xanomeline-derived M 1 agonist, 3-[3-（3-florophenyl-2-propyn- 1- ylthio）-1,2,5-thiadiazol-4-yl]-1,2,5,6- tetrahydro-1-methylpyridine Oxalate （EUK1001）, the acute toxicity and the effects on synaptic plasticity and cognition of EUK1001 were evaluated. Methods To examine the median lethal dose （LD50） of EUK1001, a wide dose range of EUK1001 was administered by p.o. and i.p. in aged mice. Furthermore, novel object recognition task and in vitro electrophysiological technique were utilized to investigate the effects of EUK1001 on recognition memory and hippocampal synaptic plasticity in aged mice. Results EUK1001 exhibited lower toxicity than xanomeline, and improved the performance of aged mice in the novel object recognition test. In addition, bath application of 1 μmol/L EUK1001 directly induced long-term potentiation in the hippocampus slices. Conclusion We conclude that EUK1001 can improve the agerelated cognitive deficits.展开更多
Objective To investigate whether estrogen modulates learning and memory and long-term potentiation （LTP） in the hippocampus of rats with Alzheimer＇s disease （AD）. Methods The rats were divided into ovariectomy （...Objective To investigate whether estrogen modulates learning and memory and long-term potentiation （LTP） in the hippocampus of rats with Alzheimer＇s disease （AD）. Methods The rats were divided into ovariectomy （OVX） and estrogen replacement therapy （ERT） groups. Rats in the ERT group received OVX, followed by ERT, while rats in the OVX group received only OVX. The rat model of AD was established by injection of 1 μL （10 μg/μL） amyloid-beta peptide 1-40（Aβ1-40） into the hippocampus. The learning and memory ability and LTP were determined by Morris water maze and electrophysiological method, respectively. Results The escape latency in Morris water maze significantly decreased in ERT group compared with that in OVX group （P 〈 0.05）. Besides, rats in ERT group exhibited a significant enhancement of the magnitude of LTP at 30 min after high-frequency stimulation （HFS）, compared with that in OVX group （P 〈 0.01）. Conclusion ERT can attenuate the cognitive deficits in the rat model of AD, and estrogen can regulate LTP and synaptic remodeling in AD rats.展开更多
文摘学习和记忆是大脑对外界有关信息获取、处理、存储和提取的过程,其所依赖的生物学基础是神经元之间通过突触相互连接形成复杂的神经网络,启动一系列生化级联反应,导致突触可塑性变化,如长时程增强（long term potential,LTP）和长时程抑制（long term depression,LTD）,其中,LTP与学习记忆的关系尤为密切。
基金the National Basic Research Development Program of China(No. 2003CB716605)National Natural Science Fundation ofChina (No. 30470711, No. 30670682)a grant from Shang-hai Science and Technology Commission (No. 05DJ14007)
文摘Objective To characterize the function of a new xanomeline-derived M 1 agonist, 3-[3-（3-florophenyl-2-propyn- 1- ylthio）-1,2,5-thiadiazol-4-yl]-1,2,5,6- tetrahydro-1-methylpyridine Oxalate （EUK1001）, the acute toxicity and the effects on synaptic plasticity and cognition of EUK1001 were evaluated. Methods To examine the median lethal dose （LD50） of EUK1001, a wide dose range of EUK1001 was administered by p.o. and i.p. in aged mice. Furthermore, novel object recognition task and in vitro electrophysiological technique were utilized to investigate the effects of EUK1001 on recognition memory and hippocampal synaptic plasticity in aged mice. Results EUK1001 exhibited lower toxicity than xanomeline, and improved the performance of aged mice in the novel object recognition test. In addition, bath application of 1 μmol/L EUK1001 directly induced long-term potentiation in the hippocampus slices. Conclusion We conclude that EUK1001 can improve the agerelated cognitive deficits.
基金supported by the National Natural Science Foundation of China (No. 30700938,30872656, 30700861, 30800451) the Natural Science Foundation of Liaoning Province, China (No. 20082078)
文摘Objective To investigate whether estrogen modulates learning and memory and long-term potentiation （LTP） in the hippocampus of rats with Alzheimer＇s disease （AD）. Methods The rats were divided into ovariectomy （OVX） and estrogen replacement therapy （ERT） groups. Rats in the ERT group received OVX, followed by ERT, while rats in the OVX group received only OVX. The rat model of AD was established by injection of 1 μL （10 μg/μL） amyloid-beta peptide 1-40（Aβ1-40） into the hippocampus. The learning and memory ability and LTP were determined by Morris water maze and electrophysiological method, respectively. Results The escape latency in Morris water maze significantly decreased in ERT group compared with that in OVX group （P 〈 0.05）. Besides, rats in ERT group exhibited a significant enhancement of the magnitude of LTP at 30 min after high-frequency stimulation （HFS）, compared with that in OVX group （P 〈 0.01）. Conclusion ERT can attenuate the cognitive deficits in the rat model of AD, and estrogen can regulate LTP and synaptic remodeling in AD rats.
