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Rab11 的减少会阻止树突分支、突触可塑性和空间记忆形成的正确发生。

Decrease of Rab11 prevents the correct dendritic arborization, synaptic plasticity and spatial memory formation.

机构信息

Universidad Nacional de Córdoba (UNC), Av. Haya de la Torre s/n Ciudad Universitaria, 5000 Córdoba, Argentina; Instituto de Investigación Médica Mercedes y Martıín Ferreyra (INIMEC-CONICET-UNC), Av. Friuli 2434, 5016 Córdoba, Argentina.

Universidad Nacional de Córdoba (UNC), Av. Haya de la Torre s/n Ciudad Universitaria, 5000 Córdoba, Argentina; Instituto A.P. de Ciencias Básicas y Aplicadas, Universidad Nacional de Villa María (UNVM), Arturo Jauretche 1555, Ciudad Universitaria, Villa María, Argentina.

出版信息

Biochim Biophys Acta Mol Cell Res. 2020 Sep;1867(9):118735. doi: 10.1016/j.bbamcr.2020.118735. Epub 2020 May 7.

Abstract

Emerging evidence shows that Rab11 recycling endosomes (REs Rab11) are essential for several neuronal processes, including the proper functioning of growth cones, synapse architecture regulation and neuronal migration. However, several aspects of REs Rab11 remain unclear, such as its sub-cellular distribution across neuronal development, contribution to dendritic tree organization and its consequences in memory formation. In this work we show a spatio-temporal correlation between the endogenous localization of REs Rab11 and developmental stage of neurons. Furthermore, Rab11-suppressed neurons showed an increase on dendritic branching (without altering total dendritic length) and misdistribution of dendritic proteins in cultured neurons. In addition, suppression of Rab11 in adult rat brains in vivo (by expressing shRab11 through lentiviral infection), showed a decrease on both the sensitivity to induce long-term potentiation and hippocampal-dependent memory acquisition. Taken together, our results suggest that REs Rab11 expression is required for a proper dendritic architecture and branching, controlling key aspects of synaptic plasticity and spatial memory formation.

摘要

新出现的证据表明,Rab11 再循环内体(REs Rab11)对于几种神经元过程至关重要,包括生长锥的正常功能、突触结构的调节以及神经元迁移。然而,REs Rab11 的几个方面仍然不清楚,例如其在神经元发育过程中的亚细胞分布、对树突组织的贡献以及对记忆形成的影响。在这项工作中,我们显示了 REs Rab11 的内源性定位与神经元发育阶段之间的时空相关性。此外,Rab11 抑制神经元显示出树突分支增加(而不改变总树突长度)和树突蛋白在培养神经元中的分布异常。此外,通过慢病毒感染表达 shRab11 在体内抑制成年大鼠大脑中的 Rab11(通过表达 shRab11),显示出长时程增强诱导和海马依赖记忆获得的敏感性降低。总之,我们的结果表明,REs Rab11 的表达对于适当的树突结构和分支是必需的,控制着突触可塑性和空间记忆形成的关键方面。

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