Abstract
Because microglia have been suggested to produce neurotrophins, we tested this ability in vitro. Rat primary microglia were found to constitutively secrete a limited amount of brain-derived neurotrophic factor (BDNF), but nerve growth factor (NGF) and neurotrophin-3 (NT-3) were undetectable in the conditioned medium. Stimulation of the cells with lipopolysaccharide (LPS) increased BDNF secretion, and induced NGF secretion. As a first step to examine this regulation system, the association of protein kinase C (PKC) was pharmacologically analyzed. A PKC activator, phorbol-12-myristate-13-acetate, enhanced the secretion of BDNF. Pre-treatment of microglia with a PKC inhibitor, bisindolylmaleimide, suppressed LPS-stimulated BDNF secretion as well as the constitutive one. These results suggest that the PKC signaling cascade is closely associated with BDNF secretion. Among PKC isoforms, PKCalpha probably plays a role in BDNF secretion, based on the results of experiments using a specific PKC activator, 1-oleoyl-2-acetyl-sn-glycerol, and a specific PKC inhibitor, Gö 6976, and by immunoblotting. Taken together, these findings suggest that the secretion of BDNF from microglia is regulated through PKCalpha-associated signal transduction mechanism.
Copyright 2001 Wiley-Liss, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies
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Brain-Derived Neurotrophic Factor / analysis
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Brain-Derived Neurotrophic Factor / immunology
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Brain-Derived Neurotrophic Factor / metabolism
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Carbazoles / pharmacology
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Carcinogens / pharmacology
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Cells, Cultured
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Cerebral Cortex / cytology
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Culture Media, Conditioned / pharmacology
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Diglycerides / pharmacology
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Enzyme Inhibitors / pharmacology
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Indoles / pharmacology
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / metabolism
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Lipopolysaccharides / pharmacology
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Maleimides / pharmacology
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Microglia / cytology*
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Microglia / drug effects
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Microglia / metabolism*
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Nerve Growth Factor / analysis
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Nerve Growth Factor / immunology
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Nerve Growth Factor / metabolism
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Nerve Growth Factors / analysis
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Nerve Growth Factors / immunology
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Nerve Growth Factors / metabolism*
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Neurotrophin 3 / analysis
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Neurotrophin 3 / immunology
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Neurotrophin 3 / metabolism
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism
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Protein Kinase C-alpha
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Rats
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Tetradecanoylphorbol Acetate / pharmacology
Substances
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Antibodies
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Brain-Derived Neurotrophic Factor
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Carbazoles
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Carcinogens
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Culture Media, Conditioned
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Diglycerides
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Enzyme Inhibitors
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Indoles
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Isoenzymes
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Lipopolysaccharides
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Maleimides
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Nerve Growth Factors
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Neurotrophin 3
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Go 6976
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1-oleoyl-2-acetylglycerol
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Nerve Growth Factor
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Protein Kinase C
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Protein Kinase C-alpha
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bisindolylmaleimide
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Tetradecanoylphorbol Acetate