Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Impaired Hippocampal Synaptic Plasticity and Enhanced Excitatory Transmission in a Novel Animal Model of Autism Spectrum Disorders with Telomerase Reverse Transcriptase Overexpression

  • Rhee, Jeehae (Department of Biological Sciences, College of Bioscience and Biotechnology, School of Medicine, Konkuk University) ;
  • Park, Kwanghoon (Department of Biological Sciences, College of Bioscience and Biotechnology, School of Medicine, Konkuk University) ;
  • Kim, Ki Chan (Department of Neuroscience and Department of Advanced Translational Medicine, School of Medicine, Konkuk University) ;
  • Shin, Chan Young (Department of Neuroscience and Department of Advanced Translational Medicine, School of Medicine, Konkuk University) ;
  • Chung, ChiHye (Department of Biological Sciences, College of Bioscience and Biotechnology, School of Medicine, Konkuk University)
  • Received : 2018.03.27
  • Accepted : 2018.04.02
  • Published : 2018.05.31
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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 $CaMKII{\alpha}$ were significantly decreased while the expression level of $CaMKII{\alpha}$ 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.

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References

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