Imipramine induces brain-derived neurotrophic factor mRNA expression in cultured astrocytes.
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.
Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan. takano@vet.osakafu-u.ac.jp
Katsura
K
Takano
Hiroshi
H
Yamasaki
Kenji
K
Kawabe
Mitsuaki
M
Moriyama
Yoichi
Y
Nakamura
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000819:agonists / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects*
D018759:Adrenergic Uptake Inhibitors; D000929:Antidepressive Agents, Tricyclic; D019208:Brain-Derived Neurotrophic Factor; C508137:Creb1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D017868:Cyclic AMP-Dependent Protein Kinases; D007099:Imipramine