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KMID : 0606920170250040374
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Biomolecules & Therapeutics
2017 Volume.25 No. 4 p.374 ~ p.382
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Sex Differences in Autism-Like Behavioral Phenotypes and Postsynaptic Receptors Expression in the Prefrontal Cortex of TERT Transgenic Mice
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Kim Ki-Chan
Cho Kyu-Suk
Yang Sung-Min
Gonzales Edson Luck
Valencia Schley
Eun Pyeong-Hwa
Choi Chang-Soon
Mabunga Darine Froy
Kim Ji-Woon
Noh Judy Kyoung-Ju
Kim Hee-JIn
Jeon Se-Jin
Han Seol-Heui
Bahn Geon-Ho
Shin Chan-Young
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Abstract
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Autism spectrum disorder (ASD) remains unexplained and untreated despite the high attention of research in recent years. Aside from its various characteristics is the baffling male preponderance over the female population. Using a validated animal model of ASD which is the telomerase reverse transcriptase overexpressing mice (TERT-tg), we conducted ASD-related behavioral assessments and protein expression experiments to mark the difference between male and females of this animal model. After statistically analyzing the results, we found significant effects of TERT overexpression in sociability, social novelty preference, anxiety, nest building, and electroseizure threshold in the males but not their female littermates. Along these differences are the male-specific increased expressions of postsynaptic proteins which are the NMDA and AMPA receptors in the prefrontal cortex. The vGluT1 presynaptic proteins, but not GAD, were upregulated in both sexes of TERT-tg mice, although it is more significantly pronounced in the male group. Here, we confirmed that the behavioral effect of TERT overexpression in mice was male-specific, suggesting that the aberration of this gene and its downstream pathways preferentially affect the functional development of the male brain, consistent with the male preponderance in ASD.
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KEYWORD
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Sex difference, TERT transgenic mice, Autism spectrum disorder, Synapse, Excitatory/Inhibitory imbalance
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