Abstract
Neurogenesis proceeds throughout life in the higher vocal center (HVC) of the adult songbird neostriatum. Testosterone induces neuronal addition and endothelial division in HVC. We asked if testosterone-induced angiogenesis might contribute importantly to HVC neuronal recruitment. Testosterone upregulated both VEGF and its endothelial receptor, VEGF-R2/Quek1/KDR, in HVC. This yielded a burst in local HVC angiogenesis. FACS-isolated HVC endothelial cells produced BDNF in a testosterone-dependent manner. In vivo, HVC BDNF rose by the third week after testosterone, lagging by over a week the rise in VEGF and VEGF-R2. In situ hybridization revealed that much of this induced BDNF mRNA was endothelial. In vivo, both angiogenesis and neuronal addition to HVC were substantially diminished by inhibition of VEGF-R2 tyrosine kinase. These findings suggest a causal interaction between testosterone-induced angiogenesis and neurogenesis in the adult forebrain.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Brain / blood supply*
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Brain / cytology
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Brain / drug effects
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Brain / growth & development*
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Brain-Derived Neurotrophic Factor / biosynthesis
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Brain-Derived Neurotrophic Factor / metabolism
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Canaries / physiology*
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Cell Division / drug effects
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Cell Division / physiology
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Cell Movement / drug effects
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Cell Movement / physiology
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Cells, Cultured
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Endothelial Growth Factors / biosynthesis
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / metabolism
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Endothelium, Vascular / physiology*
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Estrogens / pharmacology
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Female
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Lymphokines / biosynthesis
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Male
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Neovascularization, Physiologic / drug effects
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Neovascularization, Physiologic / physiology*
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Neurons / cytology*
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Neurons / drug effects
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Neurons / physiology
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Receptor Protein-Tyrosine Kinases / biosynthesis
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Receptors, Growth Factor / biosynthesis
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Receptors, Vascular Endothelial Growth Factor
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Testosterone / pharmacology
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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Brain-Derived Neurotrophic Factor
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Endothelial Growth Factors
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Estrogens
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Lymphokines
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Receptors, Growth Factor
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Testosterone
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Receptor Protein-Tyrosine Kinases
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Receptors, Vascular Endothelial Growth Factor