tetrodotoxin and Autism-Spectrum-Disorder

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.

Topics: Animals; Autism Spectrum Disorder; CA1 Region, Hippocampal; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cyclic AMP Response Element-Binding Protein; Disease Models, Animal; Excitatory Postsynaptic Potentials; Gene Expression; Hippocampus; Inhibitory Postsynaptic Potentials; Male; Maze Learning; Mice; Mice, Transgenic; Nerve Tissue Proteins; Neuronal Plasticity; Neurotoxins; Patch-Clamp Techniques; Pyramidal Cells; Recombinant Proteins; Synaptic Transmission; Telomerase; Tetrodotoxin