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. © the japanese pharmacological society.