Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice
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...
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doaj-77bbfe96b44f48d1bf8cdeb06bd397b12021-03-20T04:55:45ZengElsevierNeurobiology of Disease1095-953X2008-07-01311127132Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO miceFemke M.S. de Vrij0Josien Levenga1Herma C. van der Linde2Sebastiaan K. Koekkoek3Chris I. De Zeeuw4David L. Nelson5Ben A. Oostra6Rob Willemsen7Department of Clinical Genetics, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The NetherlandsDepartment of Clinical Genetics, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The NetherlandsDepartment of Clinical Genetics, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The NetherlandsDepartment of Neuroscience, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The NetherlandsDepartment of Neuroscience, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The NetherlandsDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030 USADepartment of Clinical Genetics, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The NetherlandsDepartment of Clinical Genetics, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands; Corresponding author. Erasmus MC, Department of Clinical Genetics, Room Ee942, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Fax: +31 10 7044736.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.http://www.sciencedirect.com/science/article/pii/S0969996108000715Fragile X syndromeSpinesDendrite branchingMPEPFenobamPrepulse inhibition of startle |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Femke M.S. de Vrij Josien Levenga Herma C. van der Linde Sebastiaan K. Koekkoek Chris I. De Zeeuw David L. Nelson Ben A. Oostra Rob Willemsen |
spellingShingle |
Femke M.S. de Vrij Josien Levenga Herma C. van der Linde Sebastiaan K. Koekkoek Chris I. De Zeeuw David L. Nelson Ben A. Oostra Rob Willemsen Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice Neurobiology of Disease Fragile X syndrome Spines Dendrite branching MPEP Fenobam Prepulse inhibition of startle |
author_facet |
Femke M.S. de Vrij Josien Levenga Herma C. van der Linde Sebastiaan K. Koekkoek Chris I. De Zeeuw David L. Nelson Ben A. Oostra Rob Willemsen |
author_sort |
Femke M.S. de Vrij |
title |
Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice |
title_short |
Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice |
title_full |
Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice |
title_fullStr |
Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice |
title_full_unstemmed |
Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice |
title_sort |
rescue of behavioral phenotype and neuronal protrusion morphology in fmr1 ko mice |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2008-07-01 |
description |
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. |
topic |
Fragile X syndrome Spines Dendrite branching MPEP Fenobam Prepulse inhibition of startle |
url |
http://www.sciencedirect.com/science/article/pii/S0969996108000715 |
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