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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
被引:14
作者:

Rhee, Jeehae
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机构:
Konkuk Univ, Coll Biosci & Biotechnol, Dept Biol Sci, Seoul 05029, South Korea Konkuk Univ, Coll Biosci & Biotechnol, Dept Biol Sci, Seoul 05029, South Korea

Park, Kwanghoon
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h-index: 0
机构:
Konkuk Univ, Coll Biosci & Biotechnol, Dept Biol Sci, Seoul 05029, South Korea Konkuk Univ, Coll Biosci & Biotechnol, Dept Biol Sci, Seoul 05029, South Korea

Kim, Ki Chan
论文数: 0 引用数: 0
h-index: 0
机构:
Konkuk Univ, Sch Med, Dept Neurosci, Seoul 05029, South Korea
Konkuk Univ, Sch Med, Dept Adv Translat Med, Seoul 05029, South Korea Konkuk Univ, Coll Biosci & Biotechnol, Dept Biol Sci, Seoul 05029, South Korea

Shin, Chan Young
论文数: 0 引用数: 0
h-index: 0
机构:
Konkuk Univ, Sch Med, Dept Neurosci, Seoul 05029, South Korea
Konkuk Univ, Sch Med, Dept Adv Translat Med, Seoul 05029, South Korea Konkuk Univ, Coll Biosci & Biotechnol, Dept Biol Sci, Seoul 05029, South Korea

Chung, ChiHye
论文数: 0 引用数: 0
h-index: 0
机构:
Konkuk Univ, Coll Biosci & Biotechnol, Dept Biol Sci, Seoul 05029, South Korea Konkuk Univ, Coll Biosci & Biotechnol, Dept Biol Sci, Seoul 05029, South Korea
机构:
[1] Konkuk Univ, Coll Biosci & Biotechnol, Dept Biol Sci, Seoul 05029, South Korea
[2] Konkuk Univ, Sch Med, Dept Neurosci, Seoul 05029, South Korea
[3] Konkuk Univ, Sch Med, Dept Adv Translat Med, Seoul 05029, South Korea
关键词:
ASD;
E/I imbalance;
long-term potentiation;
TERT;
hippocampus;
LONG-TERM POTENTIATION;
TRANSGENIC MICE;
MOUSE MODELS;
CA1;
REGION;
FVB/N MICE;
MEMORY;
IMPAIRMENTS;
BEHAVIOR;
DEFICITS;
ALPHA;
D O I:
10.14348/molcells.2018.0145
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
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.
引用
收藏
页码:486 / 494
页数:9
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