BDNF Regulates the Expression of Fragile X Mental Retardation Protein mRNA in the Hippocampus

Both fragile X mental retardation protein (FMRP) and brain-derived neurotrophic factor (BDNF) are implicated in the maturation of neurons and in the higher cognitive functions. We have investigated whether FMRP and BDNF are reciprocally regulated in neurons. Exposure of cultured hippocampal neurons...

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Main Authors: Maija Castrén, Katariina E Lampinen, Riitta Miettinen, Eija Koponen, Ilkka Sipola, Cathy E Bakker, Ben A Oostra, Eero Castrén
Format: Article
Language:English
Published: Elsevier 2002-10-01
Series:Neurobiology of Disease
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996102905449
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author Maija Castrén
Katariina E Lampinen
Riitta Miettinen
Eija Koponen
Ilkka Sipola
Cathy E Bakker
Ben A Oostra
Eero Castrén
author_facet Maija Castrén
Katariina E Lampinen
Riitta Miettinen
Eija Koponen
Ilkka Sipola
Cathy E Bakker
Ben A Oostra
Eero Castrén
author_sort Maija Castrén
collection DOAJ
description Both fragile X mental retardation protein (FMRP) and brain-derived neurotrophic factor (BDNF) are implicated in the maturation of neurons and in the higher cognitive functions. We have investigated whether FMRP and BDNF are reciprocally regulated in neurons. Exposure of cultured hippocampal neurons to BDNF, but not to NT-3, reduced FMR1 mRNA levels to 84.8% of control at 4 h and the levels were back to baseline by 24 h or 4 days. Furthermore, expression of FMR1 mRNA was reduced (82.4% of control) in vivo in the hippocampus of transgenic mice overexpressing TrkB receptors, and a small but significant (5.1%) decrease was also detected in FMRP protein levels. In contrast, the expression patterns of BDNF and TrkB mRNAs were not altered in FMRP-deficient mice compared to wild-type mice. Our data provide evidence that BDNF via TrkB signaling decreases FMRP expression and suggest a role for FMRP in BDNF-induced synaptic plasticity.
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spelling doaj.art-464ffc8ecfda4074b8d09e61e0b47f702022-12-21T22:26:56ZengElsevierNeurobiology of Disease1095-953X2002-10-01111221229BDNF Regulates the Expression of Fragile X Mental Retardation Protein mRNA in the HippocampusMaija Castrén0Katariina E Lampinen1Riitta Miettinen2Eija Koponen3Ilkka Sipola4Cathy E Bakker5Ben A Oostra6Eero Castrén7Department of Neurobiology, A. I. Virtanen Institute, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Neurology, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Psychiatry, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Clinical Genetics, Erasmus University, Rotterdam, The NetherlandsDepartment of Neurobiology, A. I. Virtanen Institute, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Neurology, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Psychiatry, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Clinical Genetics, Erasmus University, Rotterdam, The NetherlandsDepartment of Neurobiology, A. I. Virtanen Institute, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Neurology, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Psychiatry, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Clinical Genetics, Erasmus University, Rotterdam, The NetherlandsDepartment of Neurobiology, A. I. Virtanen Institute, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Neurology, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Psychiatry, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Clinical Genetics, Erasmus University, Rotterdam, The NetherlandsDepartment of Neurobiology, A. I. Virtanen Institute, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Neurology, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Psychiatry, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Clinical Genetics, Erasmus University, Rotterdam, The NetherlandsDepartment of Neurobiology, A. I. Virtanen Institute, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Neurology, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Psychiatry, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Clinical Genetics, Erasmus University, Rotterdam, The NetherlandsDepartment of Neurobiology, A. I. Virtanen Institute, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Neurology, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Psychiatry, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Clinical Genetics, Erasmus University, Rotterdam, The NetherlandsDepartment of Neurobiology, A. I. Virtanen Institute, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Neurology, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Psychiatry, University of Kuopio, FIN-70210, Kuopio, Finland; Department of Clinical Genetics, Erasmus University, Rotterdam, The NetherlandsBoth fragile X mental retardation protein (FMRP) and brain-derived neurotrophic factor (BDNF) are implicated in the maturation of neurons and in the higher cognitive functions. We have investigated whether FMRP and BDNF are reciprocally regulated in neurons. Exposure of cultured hippocampal neurons to BDNF, but not to NT-3, reduced FMR1 mRNA levels to 84.8% of control at 4 h and the levels were back to baseline by 24 h or 4 days. Furthermore, expression of FMR1 mRNA was reduced (82.4% of control) in vivo in the hippocampus of transgenic mice overexpressing TrkB receptors, and a small but significant (5.1%) decrease was also detected in FMRP protein levels. In contrast, the expression patterns of BDNF and TrkB mRNAs were not altered in FMRP-deficient mice compared to wild-type mice. Our data provide evidence that BDNF via TrkB signaling decreases FMRP expression and suggest a role for FMRP in BDNF-induced synaptic plasticity.http://www.sciencedirect.com/science/article/pii/S0969996102905449fragile X syndromeFmr1brain-derived neurotrophic factorTrkBgene expression
spellingShingle Maija Castrén
Katariina E Lampinen
Riitta Miettinen
Eija Koponen
Ilkka Sipola
Cathy E Bakker
Ben A Oostra
Eero Castrén
BDNF Regulates the Expression of Fragile X Mental Retardation Protein mRNA in the Hippocampus
Neurobiology of Disease
fragile X syndrome
Fmr1
brain-derived neurotrophic factor
TrkB
gene expression
title BDNF Regulates the Expression of Fragile X Mental Retardation Protein mRNA in the Hippocampus
title_full BDNF Regulates the Expression of Fragile X Mental Retardation Protein mRNA in the Hippocampus
title_fullStr BDNF Regulates the Expression of Fragile X Mental Retardation Protein mRNA in the Hippocampus
title_full_unstemmed BDNF Regulates the Expression of Fragile X Mental Retardation Protein mRNA in the Hippocampus
title_short BDNF Regulates the Expression of Fragile X Mental Retardation Protein mRNA in the Hippocampus
title_sort bdnf regulates the expression of fragile x mental retardation protein mrna in the hippocampus
topic fragile X syndrome
Fmr1
brain-derived neurotrophic factor
TrkB
gene expression
url http://www.sciencedirect.com/science/article/pii/S0969996102905449
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