10.3389/fncel.2019.00133.s001 Dongxue Li Dongxue Li Dongqing Jing Dongqing Jing Ziyang Liu Ziyang Liu Ying Chen Ying Chen Fang Huang Fang Huang Thomas Behnisch Thomas Behnisch Image_1_Enhanced Expression of Secreted α-Klotho in the Hippocampus Alters Nesting Behavior and Memory Formation in Mice.TIFF Frontiers 2019 klotho object recognition and location memory hippocampal formation/hippocampus passive avoidance memory anti-aging nesting behavior 2019-04-02 04:08:48 Figure https://frontiersin.figshare.com/articles/figure/Image_1_Enhanced_Expression_of_Secreted_-Klotho_in_the_Hippocampus_Alters_Nesting_Behavior_and_Memory_Formation_in_Mice_TIFF/7935227 <p>The klotho gene family consists of α-, β-, and γ-Klotho, which encode type I single-pass transmembrane proteins with large extracellular domains. α-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 α-Klotho leads to a phenotype that resembles accelerated aging, as the expression level of the α-Klotho protein in the hippocampal formation of mice decreases with age. Here, we show that intrahippocampal viral expression of secreted human α-Klotho alters social behavior and memory formation. Interestingly, overexpression of secreted human α-Klotho in the CA1 changed the nest-building behavior and improved object recognition, object location and passive avoidance memory. Moreover, α-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 α-Klotho.</p>