Journal
JOURNAL OF NEUROBIOLOGY
Volume 62, Issue 2, Pages 278-288Publisher
WILEY
DOI: 10.1002/neu.20100
Keywords
neurotrophin; dendrite; cortex; pyramidal neuron; PI3-kinase; MAP kinase
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Funding
- NIMH NIH HHS [MH60598] Funding Source: Medline
- NINDS NIH HHS [NS39993] Funding Source: Medline
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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. (C) 2004 Wiley Periodicals, Inc.
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