Source:http://linkedlifedata.com/resource/pubmed/id/16399702
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2006-1-9
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pubmed:abstractText |
Loss-of-function mutations or abnormal expression of the X-linked gene encoding methyl CpG binding protein 2 (MeCP2) cause a spectrum of postnatal neurodevelopmental disorders including Rett syndrome (RTT), nonsyndromic mental retardation, learning disability, and autism. Mice expressing a truncated allele of Mecp2 (Mecp2(308)) reproduce the motor and social behavior abnormalities of RTT; however, it is not known whether learning deficits are present in these animals. We investigated learning and memory, neuronal morphology, and synaptic function in Mecp2(308) mice. Hippocampus-dependent spatial memory, contextual fear memory, and social memory were significantly impaired in Mecp2(308) mutant males (Mecp2(308/Y)). The morphology of dendritic arborizations, the biochemical composition of synaptosomes and postsynaptic densities, and brain-derived neurotrophic factor expression were not altered in these mice. However, reduced postsynaptic density cross-sectional length was identified in asymmetric synapses of area CA1 of the hippocampus. In the hippocampus of symptomatic Mecp2(308/Y) mice, Schaffer-collateral synapses exhibited enhanced basal synaptic transmission and decreased paired-pulse facilitation, suggesting that neurotransmitter release was enhanced. Schaffer-collateral long-term potentiation (LTP) was impaired. LTP was also reduced in the motor and sensory regions of the neocortex. Finally, very early symptomatic Mecp2(308/Y) mice had increased basal synaptic transmission and deficits in the induction of long-term depression. These data demonstrate a requirement for MeCP2 in learning and memory and suggest that functional and ultrastructural synaptic dysfunction is an early event in the pathogenesis of RTT.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/HD24064,
http://linkedlifedata.com/resource/pubmed/grant/HD40301,
http://linkedlifedata.com/resource/pubmed/grant/MH57014,
http://linkedlifedata.com/resource/pubmed/grant/NS043969,
http://linkedlifedata.com/resource/pubmed/grant/NS049181,
http://linkedlifedata.com/resource/pubmed/grant/NS049442,
http://linkedlifedata.com/resource/pubmed/grant/NS13546
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1529-2401
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pubmed:author |
pubmed-author:AntalffyBarbaraB,
pubmed-author:ArancioOttavioO,
pubmed-author:ArmstrongDawnaD,
pubmed-author:AtkinsonRichardR,
pubmed-author:BattagliaFortunatoF,
pubmed-author:LevensonJonathan MJM,
pubmed-author:MorettiPaoloP,
pubmed-author:SweattJ DavidJD,
pubmed-author:TeagueRyanR,
pubmed-author:ZoghbiHuda YHY
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pubmed:issnType |
Electronic
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pubmed:day |
4
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
319-27
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:16399702-Animals,
pubmed-meshheading:16399702-Disease Models, Animal,
pubmed-meshheading:16399702-Female,
pubmed-meshheading:16399702-Learning,
pubmed-meshheading:16399702-Male,
pubmed-meshheading:16399702-Memory,
pubmed-meshheading:16399702-Memory Disorders,
pubmed-meshheading:16399702-Methyl-CpG-Binding Protein 2,
pubmed-meshheading:16399702-Mice,
pubmed-meshheading:16399702-Mice, Transgenic,
pubmed-meshheading:16399702-Mutation,
pubmed-meshheading:16399702-Neuronal Plasticity,
pubmed-meshheading:16399702-Rett Syndrome,
pubmed-meshheading:16399702-Synaptic Transmission
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pubmed:year |
2006
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pubmed:articleTitle |
Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome.
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pubmed:affiliation |
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
In Vitro,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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