title: Effect of brain-derived neurotrophic factor on activity-regulated cytoskeleton-associated protein gene expression in primary frontal cortical neurons. Comparison with NMDA and AMPA.
abstract: The effect of brain-derived neurotrophic factor (BDNF) on activity-regulated cytoskeleton-associated protein (Arc) mRNA levels in primary neuronal cultures of rat frontal cortex was characterized pharmacologically and compared to the effect on expression of c-fos, bdnf, neuritin, cox-2 as examples of other immediate early genes. BDNF induced a very strong increase (around 100 fold) in Arc mRNA and the maximal effect seen at 25 ng/ml. The effect was dose-dependent with EC50 around 1.6 ng/ml. The time profile revealed a significant effect after 25 min. BDNF also increased levels of c-Fos, neuritin and BDNF mRNA, but not COX-2 mRNA. The pharmacological profile of NMDA and AMPA-induced arc gene expression in frontal cortical neurons was compared to BDNF. NMDA and AMPA increased Arc mRNA but their maximal effect did not exceed 20-fold. The effect of AMPA was completely blocked by the NMDA receptor antagonist MK-801. Further, the relative amount of Arc mRNA compared to c-Fos mRNA was higher for BDNF, equal for NMDA and lower for AMPA. These results demonstrate BDNF to be a highly potent and efficient inducer of arc gene expression in vitro, emphasizing the role of this growth factor in synaptic plasticity in the frontal cortex.
authors.affiliation: Neurobiology Research Unit, Department of Nephrology and Endocrinology, University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Mona
authors.initials: M
authors.lastname: El-Sayed
authors.forename: Jacob
authors.initials: J
authors.lastname: Hofman-Bang
authors.forename: Jens D
authors.initials: JD
authors.lastname: Mikkelsen
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005625:Frontal Lobe / Q000166:cytology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016202:N-Methylaspartate / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013995:Time; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C092069:activity regulated cytoskeletal-associated protein; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid