Impaired Hippocampal Synaptic Plasticity and Enhanced Excitatory Transmission in a Novel Animal Model of Autism Spectrum Disorders with Telomerase Reverse Transcriptase Overexpression

• Published in: Molecules and cells Vol. 41; no. 5; pp. 486 - 494
• Main Authors: Rhee, Jeehae, Park, Kwanghoon, Kim, Ki Chan, Shin, Chan Young, Chung, ChiHye
• Format: Journal Article
• Language: English
• Published: United States Korean Society for Molecular and Cellular Biology 31.05.2018; 한국분자세포생물학회
• Subjects: Animals; Autism Spectrum Disorder - enzymology; Autism Spectrum Disorder - physiopathology; CA1 Region, Hippocampal - enzymology; CA1 Region, Hippocampal - physiology; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - biosynthesis; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - genetics; Cyclic AMP Response Element-Binding Protein - biosynthesis; Cyclic AMP Response Element-Binding Protein - genetics; Disease Models, Animal; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Gene Expression; Hippocampus - enzymology; Inhibitory Postsynaptic Potentials - drug effects; Inhibitory Postsynaptic Potentials - physiology; Male; Maze Learning - drug effects; Maze Learning - physiology; Mice; Mice, Transgenic; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Neuronal Plasticity; Neurotoxins - pharmacology; Patch-Clamp Techniques; Pyramidal Cells - drug effects; Pyramidal Cells - enzymology; Pyramidal Cells - physiology; Recombinant Proteins - metabolism; Synaptic Transmission - drug effects; Telomerase - genetics; Telomerase - physiology; Tetrodotoxin - pharmacology; 생물학; ASD; E/I imbalance; TERT; hippocampus; long-term potentiation
• ISSN: 1016-8478; 0219-1032
• DOI: 10.14348/molcells.2018.0145

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 phosphory-lated 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.