Imipramine induces brain-derived neurotrophic factor mRNA expression in cultured astrocytes

Katsura Takano, Hiroshi Yamasaki, Kenji Kawabe, Mitsuaki Moriyama, Yoichi Nakamura

Research output: Contribution to journalArticle

42 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)176-186
Number of pages11
JournalJournal of Pharmacological Sciences
Volume120
Issue number3
DOIs
Publication statusPublished - 2012
Externally publishedYes

Fingerprint

Imipramine
Brain-Derived Neurotrophic Factor
Astrocytes
Messenger RNA
Antidepressive Agents
Cyclic AMP Response Element-Binding Protein
Cyclic AMP-Dependent Protein Kinases
Neuronal Plasticity
MAP Kinase Signaling System
Tricyclic Antidepressive Agents
Mitogen-Activated Protein Kinase Kinases
Neuroglia
Transcription Factors
Neurons
Brain

Keywords

  • Antidepressant drug
  • Astrocyte
  • Brain-derived neurotrophic factor (BDNF)
  • cAMP response element binding protein (CREB)
  • Protein kinase A (PKA)

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Imipramine induces brain-derived neurotrophic factor mRNA expression in cultured astrocytes. / Takano, Katsura; Yamasaki, Hiroshi; Kawabe, Kenji; Moriyama, Mitsuaki; Nakamura, Yoichi.

In: Journal of Pharmacological Sciences, Vol. 120, No. 3, 2012, p. 176-186.

Research output: Contribution to journalArticle

Takano, Katsura ; Yamasaki, Hiroshi ; Kawabe, Kenji ; Moriyama, Mitsuaki ; Nakamura, Yoichi. / Imipramine induces brain-derived neurotrophic factor mRNA expression in cultured astrocytes. In: Journal of Pharmacological Sciences. 2012 ; Vol. 120, No. 3. pp. 176-186.
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