Enhanced Expression of Secreted α-Klotho in the Hippocampus Alters Nesting Behavior and Memory Formation in Mice
Enhanced Expression of Secreted α-Klotho in the Hippocampus Alters Nesting Behavior and Memory Formation in Mice
复制标题
海马体中分泌的 α-Klotho 的增强表达改变了小鼠的筑巢行为和记忆形成
DOI：
10.3389/fncel.2019.00133
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发表时间：
2019-04-02
影响因子：
5.3
通讯作者：
Behnisch, Thomas
中科院分区：
文献类型：
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作者：
Li, Dongxue;Jing, Dongqing;Behnisch, Thomas
克洛索（klotho）基因家族由α -、β -和γ -克洛索组成，它们编码具有大的细胞外结构域的I型单次跨膜蛋白。α -克洛索以全长的膜结合形式存在，其细胞外结构域裂解后还会以可溶形式存在。由于基因剪接，一种短的细胞外克洛索形式能够被表达和分泌。α -克洛索失活会导致一种类似于加速衰老的表型，因为小鼠海马结构中α -克洛索蛋白的表达水平随年龄增长而降低。在此，我们表明海马内病毒表达分泌型人α -克洛索会改变社会行为和记忆形成。有趣的是，在CA1区过表达分泌型人α -克洛索改变了筑巢行为，并改善了物体识别、物体位置和被动回避记忆。此外，α -克洛索过表达在对标准化刺激强度作出反应时增加了海马突触传递，改变了突触传递的双脉冲易化，并增强了依赖活动的突触可塑性。这些结果表明记忆形成受益于分泌型α -克洛索水平的提高。
The klotho gene family consists of alpha-, beta-, and gamma-Kiotho, which encode type I single-pass transmembrane proteins with large extracellular domains. alpha-Klotho exists as a full-length membrane-bound and as a soluble form after cleavage of the extracellular domain. Due to gene splicing, a short extracellular Klotho form can be expressed and secreted. Inactivation of alpha-Klotho leads to a phenotype that resembles accelerated aging, as the expression level of the alpha-Klotho protein in the hippocampal formation of mice decreases with age. Here, we show that intrahippocampal viral expression of secreted human alpha-Klotho alters social behavior and memory formation. Interestingly, overexpression of secreted human alpha-Klotho in the CA1 changed the nest-building behavior and improved object recognition, object location and passive avoidance memory. Moreover, alpha-Klotho overexpression increased hippocampal synaptic transmission in response to standardized stimulation strengths, altered paired-pulse facilitation of synaptic transmission, and enhanced activity-dependent synaptic plasticity. These results indicate that memory formation benefits from an augmented level of secreted alpha-Klotho.