Abstract
Depression is one of the most prevalent and livelihood-threatening forms of mental illnesses and the neural circuitry underlying depression remains incompletely understood. Recent studies suggest that the neuronal plasticity involved with brain-derived neurotrophic factor (BDNF) plays an important role in the recovery from depression. Some antidepressants are reported to induce BDNF expression in vivo; however, the mechanisms have been considered solely in neurons and not fully elucidated. In the present study, we evaluated the effects of imipramine, a classic tricyclic antidepressant drug, on BDNF expression in cultured rat brain astrocytes. Imipramine dose-dependently increased BDNF mRNA expression in astrocytes. The imipramine-induced BDNF increase was suppressed with inhibitors for protein kinase A (PKA) or MEK/ERK. Moreover, imipramine exposure activated transcription factor cAMP response element binding protein (CREB) in a dose-dependent manner. These results suggested that imipramine induced BDNF expression through CREB activation via PKA and/or ERK pathways. Imipramine treatment in depression might exert antidepressant action through BDNF production from astrocytes, and glial BDNF expression might be a target of developing novel antidepressants.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic Uptake Inhibitors / pharmacology*
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Animals
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Antidepressive Agents, Tricyclic / pharmacology*
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Astrocytes / cytology
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Astrocytes / drug effects*
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Astrocytes / metabolism
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Brain-Derived Neurotrophic Factor / genetics
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Brain-Derived Neurotrophic Factor / metabolism*
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Cells, Cultured
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Cyclic AMP Response Element-Binding Protein / agonists
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Cyclic AMP Response Element-Binding Protein / metabolism
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Down-Regulation / drug effects
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Embryo, Mammalian
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Hippocampus / cytology
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Hippocampus / drug effects*
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Hippocampus / metabolism
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Imipramine / pharmacology*
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MAP Kinase Signaling System / drug effects
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Nerve Tissue Proteins / agonists
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Nerve Tissue Proteins / antagonists & inhibitors
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Nerve Tissue Proteins / metabolism
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Phosphorylation / drug effects
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Protein Kinase Inhibitors / pharmacology
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Protein Processing, Post-Translational / drug effects
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Up-Regulation / drug effects*
Substances
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Adrenergic Uptake Inhibitors
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Antidepressive Agents, Tricyclic
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Brain-Derived Neurotrophic Factor
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Creb1 protein, rat
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Cyclic AMP Response Element-Binding Protein
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Nerve Tissue Proteins
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Protein Kinase Inhibitors
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RNA, Messenger
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Cyclic AMP-Dependent Protein Kinases
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Imipramine