Destabilization of cortical dendrites and spines by BDNF.
Particle-mediated gene transfer and two-photon microscopy were used to monitor the behavior of dendrites of individual cortical pyramidal neurons coexpressing green fluorescent protein (GFP) and brain-derived neurotrophic factor (BDNF). While the dendrites and spines of neurons expressing GFP alone grew modestly over 24-48 hr, coexpressing BDNF elicited dramatic sprouting of basal dendrites, accompanied by a regression of dendritic spines. Compared to GFP-transfected controls, the newly formed dendrites and spines were highly unstable. Experiments utilizing Trk receptor bodies, K252a, and overexpression of nerve growth factor (NGF) demonstrated that these effects were mediated by secreted BDNF interacting with extracellular TrkB receptors. Thus, BDNF induces structural instability in dendrites and spines, which, when restricted to particular portions of a dendritic arbor, may help translate activity patterns into specific morphological changes.
Howard Hughes Medical Institute, Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA. hwilson@neuro.duke.edu
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D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000502:physiology; D002227:Carbazoles / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D005289:Ferrets; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D026121:Indole Alkaloids; D008164:Luminescent Proteins / Q000096:biosynthesis; D020932:Nerve Growth Factor / Q000096:biosynthesis; D017966:Pyramidal Cells / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D020801:Receptor, Ciliary Neurotrophic Factor / Q000096:biosynthesis; D014162:Transfection; D014793:Visual Cortex / Q000166:cytology / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D026121:Indole Alkaloids; D008164:Luminescent Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D049452:Green Fluorescent Proteins; D020932:Nerve Growth Factor; C049985:staurosporine aglycone