PMID- 23076128 OWN - NLM STAT- MEDLINE DCOM- 20130422 LR - 20231213 IS - 1347-8648 (Electronic) IS - 1347-8613 (Linking) VI - 120 IP - 3 DP - 2012 TI - Imipramine induces brain-derived neurotrophic factor mRNA expression in cultured astrocytes. PG - 176-86 AB - 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. FAU - Takano, Katsura AU - Takano K AD - Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan. takano@vet.osakafu-u.ac.jp FAU - Yamasaki, Hiroshi AU - Yamasaki H FAU - Kawabe, Kenji AU - Kawabe K FAU - Moriyama, Mitsuaki AU - Moriyama M FAU - Nakamura, Yoichi AU - Nakamura Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121016 PL - Japan TA - J Pharmacol Sci JT - Journal of pharmacological sciences JID - 101167001 RN - 0 (Adrenergic Uptake Inhibitors) RN - 0 (Antidepressive Agents, Tricyclic) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Creb1 protein, rat) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Nerve Tissue Proteins) RN - 0 (Protein Kinase Inhibitors) RN - 0 (RNA, Messenger) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - OGG85SX4E4 (Imipramine) SB - IM MH - Adrenergic Uptake Inhibitors/*pharmacology MH - Animals MH - Antidepressive Agents, Tricyclic/*pharmacology MH - Astrocytes/cytology/*drug effects/metabolism MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Cells, Cultured MH - Cyclic AMP Response Element-Binding Protein/agonists/metabolism MH - Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/metabolism MH - Down-Regulation/drug effects MH - Embryo, Mammalian MH - Hippocampus/cytology/*drug effects/metabolism MH - Imipramine/*pharmacology MH - MAP Kinase Signaling System/drug effects MH - Nerve Tissue Proteins/agonists/antagonists & inhibitors/metabolism MH - Phosphorylation/drug effects MH - Protein Kinase Inhibitors/pharmacology MH - Protein Processing, Post-Translational/drug effects MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Wistar MH - Up-Regulation/*drug effects EDAT- 2012/10/19 06:00 MHDA- 2013/04/23 06:00 CRDT- 2012/10/19 06:00 PHST- 2012/10/19 06:00 [entrez] PHST- 2012/10/19 06:00 [pubmed] PHST- 2013/04/23 06:00 [medline] AID - DN/JST.JSTAGE/jphs/12039FP [pii] AID - 10.1254/jphs.12039fp [doi] PST - ppublish SO - J Pharmacol Sci. 2012;120(3):176-86. doi: 10.1254/jphs.12039fp. Epub 2012 Oct 16.