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The Journal of Neuroscience, November 15, 2002, 22(22):9754-9763

Increased Expression of Brain-Derived Neurotrophic Factor Induces Formation of Basal Dendrites and Axonal Branching in Dentate Granule Cells in Hippocampal Explant Cultures

Steve C. Danzer¹, Kristy R. C. Crooks², Donald C. Lo², and James O. McNamara^{1, 2, 3, 4}

Departments of ¹ Medicine (Neurology), ² Neurobiology, ³ Pharmacology, and ⁴ Molecular Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710

During limbic epileptogenesis in vivo the dentate granule cells (DGCs) exhibit increased expression of brain-derived neurotrophic factor (BDNF), followed by striking morphologic plasticities, namely the formation of basal dendrites and the sprouting of mossy fibers. We hypothesized that increased expression of BDNF intrinsic to DGCs is sufficient to induce these plasticities. To test this hypothesis, we transfected DGCs in rat hippocampal slice cultures with BDNF or nerve growth factor (NGF) via particle-mediated gene transfer, and we visualized the neuronal processes with cotransfected green fluorescent protein. Transfection with BDNF produced significant increases in axonal branch and basal dendrite number relative to NGF or empty vector controls. Structural changes were prevented by the tyrosine kinase inhibitor K252a. Thus increased expression of BDNF within DGCs is sufficient to induce these morphological plasticities, which may represent one mechanism by which BDNF promotes limbic epileptogenesis.

Key words: dentate granule cell; basal dendrite; mossy fiber sprouting; BDNF; epileptogenesis; biolistics

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22229754-10$05.00/0

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