Serum- and glucocorticoid-inducible kinase 1 activity reduces dendritic spines in dorsal hippocampus.
Serum- and glucocorticoid-inducible kinase 1 activity reduces dendritic spines in dorsal hippocampus.
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血清和糖皮质激素诱导激酶 1 活性减少背侧海马的树突棘。
DOI：
10.1016/j.neulet.2020.134909
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发表时间：
2020
影响因子：
2.5
通讯作者：
Robison,AlfredJ
中科院分区：
文献类型：
--
作者：
Steffke,EmilyE;Kirca,Deniz;Mazei-Robison,MichelleS;Robison,AlfredJ
众所周知，海马体在调节学习和记忆方面具有重要作用，其功能可直接受到应激和糖皮质激素受体激活的调节。海马对学习的贡献被认为依赖于特定亚区突触可塑性的变化，而这些功能变化伴随着树突棘数量和形状的形态学变化，这些树突棘是这些谷氨酸突触的物理相关性。血清和糖皮质激素诱导激酶1 （SGK1）调节前额皮质树突棘形态，小鼠海马SGK1表达的调节调节学习。然而，SGK1在海马CA1和齿状回区域内树突棘形态中的作用尚不清楚。因此，将表达GFP和各种SGK1构建物的单纯疱疹病毒载体（包括野生型SGK1、催化无活性版本的SGK1 （K127Q）和磷酸化缺陷版本的SGK1 (S78A)）注入成年小鼠海马中，并使用共聚焦荧光显微镜观察树突棘。我们发现，齿状回中SGK1表达的增加增加了棘的总数，这主要是由于蘑菇棘的增加，而CA1区域SGK1活性（K127Q）的降低增加了树突棘的总数，这主要是由于蘑菇和短棍棘的显著增加。SGK1在这些区域的不同作用可能是由SGK1与脊柱形成和稳定所需的多种途径相互作用介导的。由于成熟突触的形成是学习和记忆的重要组成部分，这表明SGK1是认知和记忆中应激相关变化通路的潜在靶点。
The hippocampus has a well-known role in mediating learning and memory, and its function can be directly regulated by both stress and glucocorticoid receptor activation. Hippocampal contributions to learning are thought to be dependent on changes in the plasticity of synapses within specific subregions, and these functional changes are accompanied by morphological changes in the number and shape of dendritic spines, the physical correlates of these glutamatergic synapses. Serum- and glucocorticoid-inducible kinase 1 (SGK1) regulates dendritic spine morphology in the prefrontal cortex, and modulation of SGK1 expression in mouse hippocampus regulates learning. However, the role of SGK1 in dendritic spine morphology within the CA1 and dentate gyrus regions of the hippocampus are unknown. Thus, herpes simplex viral vectors expressing GFP and various SGK1 constructs, including wild type SGK1, a catalytically inactive version of SGK1 (K127Q), and a phospho-defective version of SGK1 (S78A), were infused into the hippocampus of adult mice and confocal fluorescent microscopy was used to visualize dendritic spines. We show that increasing expression of SGK1 in the dentate gyrus increased the total number of spines, driven primarily by an increase in mushroom spines, while decreasing SGK1 activity (K127Q) in the CA1 region increased the total number of dendritic spines, driven by a significant increase in mushroom and stubby spines. The differential effects of SGK1 in these regions may be mediated by the interactions of SGK1 with multiple pathways required for spine formation and stability. As the formation of mature synapses is a crucial component of learning and memory, this indicates that SGK1 is a potential target in the pathway underlying stress-associated changes in cognition and memory.
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DOI：
--
发表时间：
1991
期刊：
影响因子：
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DOI：
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通讯作者：
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DOI：
--
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1983
期刊：
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