Imipramine Induces Brain-Derived Neurotrophic Factor mRNA Expression in Cultured Astrocytes

Journal of Pharmacological Sciences

Mitsuaki Moriyama¹  Kenji Kawabe¹  Katsura Takano¹  Yoichi Nakamura¹  Hiroshi Yamasaki¹ 

[1] Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, Japan

关键词: astrocyte;    antidepressant drug;    brain-derived neurotrophic factor (BDNF);    protein kinase A (PKA);    cAMP response element binding protein (CREB);   

DOI  :  10.1254/jphs.12039FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(49)Cited-By(19)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.

【 授权许可】

Unknown