Abstract
Dendritic arbor development of subventricular zone-derived interneurons is a critical step in their integration into functional circuits of the postnatal olfactory bulb. However, the mechanism and molecular control of this process remain unknown. In this study, we have developed a culture model where dendritic development of purified subventricular zone cells proceeds under serum-free conditions in the absence of added growth factors and non-neural cells. We demonstrate that the large majority of these cells in culture express GABA and elaborate dendritic arbors with spine-like protrusions but they do not possess axons. These neurons expressed receptors for neurotrophins including p75, TrkB and TrkC but not TrkA. Application of exogenous neurotrophins, including brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) and nerve growth factor (NGF), to cultures stimulated dendritic growth and led to more complex dendritic arbors during the initial 3 days in culture. Our results suggest that these effects are independent of Trk receptors and mediated by the p75/ceramide signaling pathway. We also show that brain-derived neurotrophic factor is the only neurotrophin that is able to influence late-phase dendritic development via TrkB receptor activation. These results suggest that dendritic arbor development of subventricular zone-derived cells may be regulated by neurotrophins through the activation of p75 and the TrkB receptor signaling pathways in a sequentially defined temporal pattern.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism
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Animals
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Animals, Newborn
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Brain-Derived Neurotrophic Factor / pharmacology
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Cell Death
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Cells, Cultured
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Cerebral Ventricles / cytology*
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DNA, Complementary / biosynthesis
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Dendrites / drug effects
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Dendrites / physiology*
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Diagnostic Imaging / methods
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GAP-43 Protein / metabolism
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Immunohistochemistry / methods
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In Situ Nick-End Labeling / methods
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Intermediate Filament Proteins / metabolism
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Microtubule-Associated Proteins / metabolism
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Nerve Growth Factor / pharmacology
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Nerve Tissue Proteins / metabolism
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Nestin
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Neural Cell Adhesion Molecule L1 / metabolism
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Neurons / drug effects
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Neurons / physiology*
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Neurotrophin 3 / pharmacology
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Polymerase Chain Reaction / methods
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Proto-Oncogene Proteins c-fos / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptor, Nerve Growth Factor
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Receptor, trkA / metabolism
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Receptor, trkB / metabolism*
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Receptors, Nerve Growth Factor / metabolism*
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Sialic Acids / metabolism
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Stem Cells / physiology*
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Time Factors
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Tubulin / metabolism
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gamma-Aminobutyric Acid / metabolism
Substances
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Actins
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Brain-Derived Neurotrophic Factor
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DNA, Complementary
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GAP-43 Protein
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Intermediate Filament Proteins
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MAP2 protein, rat
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Microtubule-Associated Proteins
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Nerve Tissue Proteins
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Nes protein, rat
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Nestin
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Neural Cell Adhesion Molecule L1
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Neurotrophin 3
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Proto-Oncogene Proteins c-fos
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Receptor, Nerve Growth Factor
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Receptors, Nerve Growth Factor
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Sialic Acids
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Tubb3 protein, rat
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Tubulin
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polysialyl neural cell adhesion molecule
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gamma-Aminobutyric Acid
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Nerve Growth Factor
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Receptor, trkA
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Receptor, trkB