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 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.
Castrén
Maija
M
Department of Neurobiology, A. I. Virtanen Institute, University of Kuopio, FIN-70210 Kuopio, Finland.
Lampinen
Katariina E
KE
Miettinen
Riitta
R
Koponen
Eija
E
Sipola
Ilkka
I
Bakker
Cathy E
CE
Oostra
Ben A
BA
Castrén
Eero
E
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D051860:Fragile X Messenger Ribonucleoprotein 1; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020933:Neurotrophin 3 / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins; D020813:Receptor, trkB / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D020813:Receptor, trkB; C497684:Fmr1 protein, mouse