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 r...

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Main Authors: Katsura Takano, Hiroshi Yamasaki, Kenji Kawabe, Mitsuaki Moriyama, Yoichi Nakamura
Format: Article
Language:English
Published: Elsevier 2012-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319304323
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author Katsura Takano
Hiroshi Yamasaki
Kenji Kawabe
Mitsuaki Moriyama
Yoichi Nakamura
author_facet Katsura Takano
Hiroshi Yamasaki
Kenji Kawabe
Mitsuaki Moriyama
Yoichi Nakamura
author_sort Katsura Takano
collection DOAJ
description 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. Keywords:: astrocyte, antidepressant drug, brain-derived neurotrophic factor (BDNF), protein kinase A (PKA), cAMP response element binding protein (CREB)
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spelling doaj.art-e9dc1a8257c946c7a6fc6c962824691d2022-12-22T03:04:25ZengElsevierJournal of Pharmacological Sciences1347-86132012-01-011203176186Imipramine Induces Brain-Derived Neurotrophic Factor mRNA Expression in Cultured AstrocytesKatsura Takano0Hiroshi Yamasaki1Kenji Kawabe2Mitsuaki Moriyama3Yoichi Nakamura4Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, 1-58, Rinku-Ourai Kita, Izumisano, Osaka 598-8531, Japan; Corresponding author. takano@vet.osakafu-u.ac.jpLaboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, 1-58, Rinku-Ourai Kita, Izumisano, Osaka 598-8531, JapanLaboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, 1-58, Rinku-Ourai Kita, Izumisano, Osaka 598-8531, JapanLaboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, 1-58, Rinku-Ourai Kita, Izumisano, Osaka 598-8531, JapanLaboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, 1-58, Rinku-Ourai Kita, Izumisano, Osaka 598-8531, JapanDepression 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. Keywords:: astrocyte, antidepressant drug, brain-derived neurotrophic factor (BDNF), protein kinase A (PKA), cAMP response element binding protein (CREB)http://www.sciencedirect.com/science/article/pii/S1347861319304323
spellingShingle Katsura Takano
Hiroshi Yamasaki
Kenji Kawabe
Mitsuaki Moriyama
Yoichi Nakamura
Imipramine Induces Brain-Derived Neurotrophic Factor mRNA Expression in Cultured Astrocytes
Journal of Pharmacological Sciences
title Imipramine Induces Brain-Derived Neurotrophic Factor mRNA Expression in Cultured Astrocytes
title_full Imipramine Induces Brain-Derived Neurotrophic Factor mRNA Expression in Cultured Astrocytes
title_fullStr Imipramine Induces Brain-Derived Neurotrophic Factor mRNA Expression in Cultured Astrocytes
title_full_unstemmed Imipramine Induces Brain-Derived Neurotrophic Factor mRNA Expression in Cultured Astrocytes
title_short Imipramine Induces Brain-Derived Neurotrophic Factor mRNA Expression in Cultured Astrocytes
title_sort imipramine induces brain derived neurotrophic factor mrna expression in cultured astrocytes
url http://www.sciencedirect.com/science/article/pii/S1347861319304323
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