Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice

被引：252

作者：

de Vrij, Fernke M. S. ^{[1
]}

Levenga, Josien ^{[1
]}

Van der Linde, Herma C. ^{[1
]}

Koekkoek, Sebastiaan K. ^{[2
]}

De Zeeuw, Chris I. ^{[2
]}

Nelson, David L. ^{[3
]}

Oostra, Ben A. ^{[1
]}

Willemsen, Rob ^{[1
]}

机构：

[1] Erasmus MC, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands

[2] Erasmus MC, Dept Neurosci, NL-3015 GE Rotterdam, Netherlands

[3] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

来源：

NEUROBIOLOGY OF DISEASE | 2008年 / 31卷 / 01期

关键词：

Fragile X Syndrome; spines; dendrite branching; MPEP; fenobam; prepulse inhibition of startle; metabotropic glutamate receptor; primary hippocampal neuron culture;

D O I：

10.1016/j.nbd.2008.04.002

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Lack of fragile X mental retardation protein (FMRP) causes Fragile X Syndrome, the most common form of inherited mental retardation. FMRP is an RNA-binding protein and is a component of messenger ribonucleoprotein complexes, associated with brain polyribosomes, including dendritic polysomes. FMRP is therefore thought to be involved in translational control of specific mRNAs at synaptic sites. In mice lacking FMRP, protein synthesis-dependent synaptic plasticity is altered and structural malformations of dendritic protrusions occur. One hypothesized cause of the disease mechanism is based on exaggerated group I mGluR receptor activation. In this study, we examined the effect of the mGluR5 antagonist MPEP on Fragile X related behavior in Fmr1 KO mice. Our results demonstrate a clear defect in prepulse inhibition of startle in Fmr1 KO mice, that could be rescued by MPEP. Moreover, we show for the first time a structural rescue of Fragile X related protrusion morphology with two independent mGluR5 antagonists. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：127 / 132

页数：6

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