Impaired Hippocampal Synaptic Plasticity and Enhanced Excitatory Transmission in a Novel Animal Model of Autism Spectrum Disorders with Telomerase Reverse Transcriptase Overexpression
Jeehae Rhee1,3, Kwanghoon Park1,3, Ki Chan Kim2, Chan Young Shin2, and ChiHye Chung1,*
1Department of Biological Sciences, College of Bioscience and Biotechnology, 2Department of Neuroscience and Department of
Advanced Translational Medicine, School of Medicine, Konkuk University, Seoul 05029, Korea, 3These authors equally contributed
to this work.
*Correspondence: cchung@konkuk.ac.kr
Received March 27, 2018; Accepted April 2, 2018.; Published online April 26, 2018.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

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ABSTRACT
Recently, we have reported that animals with telomerase reverse transcriptase (TERT) overexpression exhibit reduced social interaction, decreased preference for novel social interaction and poor nest-building behaviors—symptoms that mirror those observed in human autism spectrum disorders (ASD). Overexpression of TERT also alters the excitatory/inhibitory (E/I) ratio in the medial prefrontal cortex. However, the effects of TERT overexpression on hippocampal-dependent learning and synaptic efficacy have not been investigated. In the present study, we employed electrophysiological approaches in combination with behavioral analysis to examine hippocampal function of TERT transgenic (TERT-tg) mice and FVB controls. We found that TERT overexpression results in enhanced hippocampal excitation with no changes in inhibition and significantly impairs long-term synaptic plasticity. Interestingly, the expression levels of phosphorylated CREB and phosphorylated CaMKIIα were significantly decreased while the expression level of CaMKIIα was slightly increased in the hippocampus of TERT-overexpressing mice. Our observations highlight the importance of TERT in normal synaptic function and behavior and provide additional information on a novel animal model of ASD associated with TERT overexpression.
Keywords: ASD, E/I imbalance, long-term potentiation, TERT,
hippocampus


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30 April 2018 Volume 41,
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