目的探讨N-甲基-D-天门冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR or NR)亚基NR2A在脑缺血再灌注引起的海马CA1区神经元树突棘丢失和认知功能障碍中的作用。方法制作三动脉阻断(3-VO)GFP转基因小鼠全脑缺血模型,小鼠随机分为假...目的探讨N-甲基-D-天门冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR or NR)亚基NR2A在脑缺血再灌注引起的海马CA1区神经元树突棘丢失和认知功能障碍中的作用。方法制作三动脉阻断(3-VO)GFP转基因小鼠全脑缺血模型,小鼠随机分为假手术组、脑缺血再灌注(I/R)组和NVP-AAM077(NVP)干预组;应用跳台试验测试小鼠学习记忆能力,激光共聚焦和Neurolucida软件分析检测海马CA1区神经元形态及树突棘的变化。结果学习记忆能力测试发现,I/R组明显差于sham组(P<0.05),NVP干预组差于sham组和I/R组(P<0.05);I/R组CA1区神经元树突棘的数量明显少于假手术组(P<0.01),NVP干预能进一步增加缺血/再灌注所致的CA1区神经元树突棘的丢失(P<0.05)。结论 NMDA受体亚基NR2A在小鼠脑缺血再灌注所致树突棘丢失和脑认知功能损害中具有重要作用。展开更多
Postmitotic neurons in the developing cortex migrate along radial glial fibers to their proper location in the cortical plate and form the layered structure.Here we report that the radial migration of rat layer II/III...Postmitotic neurons in the developing cortex migrate along radial glial fibers to their proper location in the cortical plate and form the layered structure.Here we report that the radial migration of rat layer II/III cortical neurons requires guidance by the extracellular diffusible factor Semaphorin-3A(Sema3A).This factor is expressed in a descending gradient across the cortical layers,whereas its receptor neuropilin-1(NP1)is highly expressed in migrating neurons.Downregulation or conditional knockout of NP1 in newborn cortical neurons impedes their radial migration by disrupting their radial orientation during migration without altering their cell fate.Studies in cultured cortical slices further show that the endogenous gradient of Sema3A is required for the proper migration of newborn neurons.In addition,transwell chemotaxis assays show that isolated newborn neurons are attracted by Sema3A.Thus,Sema3A may function as a chemoattractive guidance signal for the radial migration of newborn cortical neurons toward upper layers.展开更多
文摘目的探讨N-甲基-D-天门冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR or NR)亚基NR2A在脑缺血再灌注引起的海马CA1区神经元树突棘丢失和认知功能障碍中的作用。方法制作三动脉阻断(3-VO)GFP转基因小鼠全脑缺血模型,小鼠随机分为假手术组、脑缺血再灌注(I/R)组和NVP-AAM077(NVP)干预组;应用跳台试验测试小鼠学习记忆能力,激光共聚焦和Neurolucida软件分析检测海马CA1区神经元形态及树突棘的变化。结果学习记忆能力测试发现,I/R组明显差于sham组(P<0.05),NVP干预组差于sham组和I/R组(P<0.05);I/R组CA1区神经元树突棘的数量明显少于假手术组(P<0.01),NVP干预能进一步增加缺血/再灌注所致的CA1区神经元树突棘的丢失(P<0.05)。结论 NMDA受体亚基NR2A在小鼠脑缺血再灌注所致树突棘丢失和脑认知功能损害中具有重要作用。
基金supported by the National Natural Science Foundation of China (No. 30900430)Scientific Research Fund of Education Department of Zhejiang Provincie, China (No. Y200803366)+3 种基金Ningbo Natural Science Foundation (No. 2009A610119)Talent Project of Ningbo University (No. RCL2008008)Scientific Research Fund of Ningbo University (No. xkl09125)K. C. Wong Magna Fund
文摘Postmitotic neurons in the developing cortex migrate along radial glial fibers to their proper location in the cortical plate and form the layered structure.Here we report that the radial migration of rat layer II/III cortical neurons requires guidance by the extracellular diffusible factor Semaphorin-3A(Sema3A).This factor is expressed in a descending gradient across the cortical layers,whereas its receptor neuropilin-1(NP1)is highly expressed in migrating neurons.Downregulation or conditional knockout of NP1 in newborn cortical neurons impedes their radial migration by disrupting their radial orientation during migration without altering their cell fate.Studies in cultured cortical slices further show that the endogenous gradient of Sema3A is required for the proper migration of newborn neurons.In addition,transwell chemotaxis assays show that isolated newborn neurons are attracted by Sema3A.Thus,Sema3A may function as a chemoattractive guidance signal for the radial migration of newborn cortical neurons toward upper layers.
基金supported by the National Basic Research Program (973 Program) (No. 2011CBA00400 and 2006CB806600)the National Natural Science Foundation of China (No. 31025012)+1 种基金the Shanghai Pujiang Program (No. 07PJ14108)the Hundreds of Talents Program and the Knowledge Innovation Project from Chinese Academy of Sciences (No. KSCX2-YW-R-102)
