BDNF regulates primary dendrite formation in cortical neurons via the PI3-kinase and MAP kinase signaling pathways.
Neurotrophins are known to regulate dendritic development, but the mechanisms that mediate neurotrophin-dependent dendrite formation are largely unknown. Here we show that brain-derived neurotrophic factor (BDNF) induces the formation of primary dendrites in cortical neurons by a protein synthesis-independent mechanism. BDNF leads to the rapid activation of PI3-kinase, MAP kinase, and PLC-gamma in cortical neurons, and pharmacological inhibition of PI3-kinase and MAP kinase in dissociated cell cultures and cortical slice cultures suppresses the ability of BDNF to induce dendrite formation. A constitutively active form of PI3-kinase, but not MEK, is sufficient to induce primary dendrite formation in cortical neurons. These observations indicate that BDNF induces primary dendrite formation via activation of the PI3-kinase and MAP kinase pathways and provide insight into the mechanisms that mediate the morphological effects of neurotrophin signaling.
Dijkhuizen
Paul A
PA
Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland 21205, USA.
Ghosh
Anirvan
A
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D003712:Dendrites / Q000187:drug effects* / Q000502:physiology; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D005455:Fluorescent Antibody Technique / Q000379:methods; D049452:Green Fluorescent Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors; D014162:Transfection / Q000379:methods
D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D049452:Green Fluorescent Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors