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 [1 ]
Park, Kwanghoon [1 ]
Kim, Ki Chan [2 ,3 ]
Shin, Chan Young [2 ,3 ]
Chung, ChiHye [1 ]
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
相关论文
共 50 条
[11]   Multipotential nestin and Isl-1 positive mesenchymal stem cells isolated from human pancreatic islets [J].
Eberhardt, Michael ;
Salmon, Patrick ;
Von Mach, Marc-Alexander ;
Hengstler, Jan Georg ;
Brulport, Marc ;
Linscheid, Philippe ;
Seboek, Dalma ;
Oberholzer, Jose ;
Barbero, Andrea ;
Martin, Ivan ;
Mueller, Beat ;
Trono, Didier ;
Zulewski, Henryk .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 345 (03) :1167-1176
[12]   Spatial cognition in autism spectrum disorders: Superior, impaired, or just intact? [J].
Edgin, JO ;
Pennington, BF .
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS, 2005, 35 (06) :729-745
[13]   FVB.129P2-Pde6b+ Tyrc-ch/Ant, a sighted variant of the FVB/N mouse strain suitable for behavioral analysis [J].
Errijgers, V. ;
Van Dam, D. ;
Gantois, I. ;
Van Ginneken, C. J. ;
Grossman, A. W. ;
D'Hooge, R. ;
De Deyn, P. P. ;
Kooy, R. F. .
GENES BRAIN AND BEHAVIOR, 2007, 6 (06) :552-557
[14]   Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function [J].
Etherton, Mark ;
Foeldy, Csaba ;
Sharma, Manu ;
Tabuchi, Katsuhiko ;
Liu, Xinran ;
Shamloo, Mehrdad ;
Malenka, Robert C. ;
Suedhof, Thomas C. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (33) :13764-13769
[15]   Mouse neurexin-1α deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments [J].
Etherton, Mark R. ;
Blaiss, Cory A. ;
Powell, Craig M. ;
Suedhof, Thomas C. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (42) :17998-18003
[16]   Reevaluating Hippocampus-Dependent Learning in FVB/N Mice [J].
Farley, Sean J. ;
McKay, Bridget M. ;
Disterhoft, John F. ;
Weiss, Craig .
BEHAVIORAL NEUROSCIENCE, 2011, 125 (06) :871-878
[17]   Memantine restores long term potentiation impaired by tonic N-methyl-D-aspartate (NMDA) receptor activation following reduction of Mg2+ in hippocampal slices [J].
Frankiewicz, T ;
Parsons, CG .
NEUROPHARMACOLOGY, 1999, 38 (09) :1253-1259
[18]   Neuroprotective effects of docosahexaenoic acid on hippocampal cell death and learning and memory impairments in a valproic acid-induced rat autism model [J].
Gao, Jingquan ;
Wang, Xuelai ;
Sun, Hongli ;
Cao, Yonggang ;
Liang, Shuang ;
Wang, Han ;
Wang, Yanming ;
Yang, Feng ;
Zhang, Fengyu ;
Wu, Lijie .
INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, 2016, 49 :67-78
[19]   Common circuit defect of excitatory-inhibitory balance in mouse models of autism [J].
Gogolla, Nadine ;
LeBlanc, Jocelyn J. ;
Quast, Kathleen B. ;
Sudhof, Thomas C. ;
Fagiolini, Michela ;
Hensch, Takao K. .
JOURNAL OF NEURODEVELOPMENTAL DISORDERS, 2009, 1 (02) :172-181
[20]   Correlative memory deficits, A beta elevation, and amyloid plaques in transgenic mice [J].
Hsiao, K ;
Chapman, P ;
Nilsen, S ;
Eckman, C ;
Harigaya, Y ;
Younkin, S ;
Yang, FS ;
Cole, G .
SCIENCE, 1996, 274 (5284) :99-102