Nectin-3 modulates the structural plasticity of dentate granule cells and long-term memory.
Nectin-3 modulates the structural plasticity of dentate granule cells and long-term memory.
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Nectin-3 调节齿状颗粒细胞的结构可塑性和长期记忆
DOI：
10.1038/tp.2017.196
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发表时间：
2017-09-05
影响因子：
6.8
通讯作者：
Wang XD
中科院分区：
文献类型：
--
作者：
Wang XX;Li JT;Xie XM;Gu Y;Si TM;Schmidt MV;Wang XD
Nectin-3是一种在海马神经元中富集的细胞粘附分子，与应激相关的认知障碍有关。Nectin-3由齿状回（DG）的颗粒细胞表达，但DG中的Nectin-3是否调节齿状回颗粒细胞的结构可塑性和海马依赖性记忆仍不清楚。在这项研究中，我们发现，DG nectin-3的表达水平的发育调控和减少出生后早期应激暴露在成年小鼠。最重要的是，腺相关病毒（腺相关病毒）敲低所有DG神经元群体中的nectin-3水平模拟了早期生活压力的认知影响，并损害了长期空间记忆和时间顺序记忆。此外，AAV介导的DG nectin-3敲低增加了增殖下的doublecortin免疫反应性分化细胞和calretinin免疫反应性未成熟神经元的密度，但显著降低了calbindin免疫反应性，表明nectin-3调节成年出生的DG颗粒细胞的分化和成熟。使用逆转录病毒靶向新产生的DG神经元，我们发现，选择性nectin-3敲低新DG神经元也损害长期空间记忆。此外，抑制新DG神经元中的nectin-3表达引起树突棘减少，特别是细棘。我们的数据表明，在DG神经元中表达的nectin-3可以调节成年神经发生，树突棘可塑性和早期生活压力的认知效应。
Nectin-3, a cell adhesion molecule enriched in hippocampal neurons, has been implicated in stress-related cognitive disorders. Nectin-3 is expressed by granule cells in the dentate gyrus (DG), but it remains unclear whether nectin-3 in DG modulates the structural plasticity of dentate granule cells and hippocampus-dependent memory. In this study, we found that DG nectin-3 expression levels were developmentally regulated and reduced by early postnatal stress exposure in adult mice. Most importantly, knockdown of nectin-3 levels in all DG neuron populations by adeno-associated virus (AAV) mimicked the cognitive effects of early-life stress, and impaired long-term spatial memory and temporal order memory. Moreover, AAV-mediated DG nectin-3 knockdown increased the density of doublecortin-immunoreactive differentiating cells under proliferation and calretinin-immunoreactive immature neurons, but markedly decreased calbindin immunoreactivity, indicating that nectin-3 modulates the differentiation and maturation of adult-born DG granule cells. Using retrovirus to target newly generated DG neurons, we found that selective nectin-3 knockdown in new DG neurons also impaired long-term spatial memory. In addition, suppressing nectin-3 expression in new DG neurons evoked a reduction of dendritic spines, especially thin spines. Our data indicate that nectin-3 expressed in DG neurons may modulate adult neurogenesis, dendritic spine plasticity and the cognitive effects of early-life stress.
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DOI：
10.1523/jneurosci.4185-12.2013
发表时间：
2013-02-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Hodge RD;Garcia AJ 3rd;Elsen GE;Nelson BR;Mussar KE;Reiner SL;Ramirez JM;Hevner RF
通讯作者：
Hevner RF
影响因子：
25
作者：
Mirescu, C;Peters, JD;Gould, E
通讯作者：
Gould, E
DOI：
10.3791/1543
发表时间：
2009-11-17
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Hagihara, Hideo;Toyama, Keiko;Miyakawa, Tsuyoshi
通讯作者：
Miyakawa, Tsuyoshi
阻断促肾上腺皮质激素释放激素受体 1 可减轻生命早期应激引起的新生儿海马突触异常
影响因子：
3.5
作者：
Liao, Xue-Mei;Yang, Xiao-Dun;Wang, Xiao-Dong
通讯作者：
Wang, Xiao-Dong
影响因子：
2.7
作者：
Bagot, Rosemary C.;van Hasselt, Felisa N.;Joels, Marian
通讯作者：
Joels, Marian