title: Metabotropic glutamate receptor 2 and corticotrophin-releasing factor receptor-1 gene expression is differently regulated by BDNF in rat primary cortical neurons.
abstract: Brain-derived neurotrophic factor (BDNF) is important for neuronal survival and plasticity. Incorporation of matured receptor proteins is an integral part of synapse formation. However, whether BDNF increases synthesis and integration of receptors in functional synapses directly is unclear. We are particularly interested in the regulation of the 5-hydroxytryptamine receptor 2A (5-HT(2A)R). This receptor form a functional complex with the metabotropic glutamate receptor 2 (mGluR2) and is recruited to the cell membrane by the corticotrophin-releasing factor receptor 1 (CRF-R1). The effect of BDNF on gene expression for all these receptors, as well as a number of immediate-early genes, was pharmacologically characterized in primary neurons from rat frontal cortex. BDNF increased CRF-R1 mRNA levels up to fivefold, whereas mGluR2 mRNA levels were proportionally downregulated. No effect on 5-HT(2A)R mRNA was seen. The effects were dose-dependent with half-maximal effective concentrations (EC(50)) around 1 ng/ml. After 24 h of incubation with BDNF, CRF-R1 mRNA levels had returned to baseline levels, whereas mGluR2 mRNA levels remained low. A significant reduction of all three receptor transcripts was observed after neuronal depolarization produced by high potassium. This study emphasizes the role of BDNF as an important regulator of receptor compositions in the synapse and provides further evidence that BDNF directly regulates important drug targets involved in cognition and mood.
authors.affiliation: Neurobiology Research Unit, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Christinna V
authors.initials: CV
authors.lastname: Jørgensen
authors.forename: Anders B
authors.initials: AB
authors.lastname: Klein
authors.forename: Mona
authors.initials: M
authors.lastname: El-Sayed
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
authors.forename: Jens D
authors.initials: JD
authors.lastname: Mikkelsen
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D005625:Frontal Lobe / Q000378:metabolism*; D005786:Gene Expression Regulation; D017781:Genes, Immediate-Early; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D014158:Transcription, Genetic; D000099052:CRF Receptor, Type 1
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D018019:Receptors, Corticotropin-Releasing Hormone; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; D000099052:CRF Receptor, Type 1; D011188:Potassium
keywords: corticotrophin-releasing factor receptor-1 (CRF-R1); metabotropic glutamate receptor 2 (mGluR2); receptor regulation; serotonin receptor 2A (5-HT2AR); synapse