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

Abstract

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.

Role of p38MAPK in S1P receptor-mediated differentiation of human oligodendrocyte progenitors

“…These results suggest that the FTY720-p-induced OPC differentiation in our isolated cultures or in co-cultures with DRGNs may be partly mediated by astrocytes. This is consistent with data showing that both CREB and ERK1/2 are involved in the release of neurotrophic factors BDNF, NT-3, and CNTF from astrocytes (Corbett et al, 2013;Modi et al, 2013;Paintlia et al, 2013;Takano et al, 2012), and these secreted factors in turn could enhance OPC differentiation.…”

An astroglial basis of major depressive disorder? An overview

“…Although neurons are generally regarded as the major source of BDNF, glial cells, including astrocytes and microglia, also possess the ability to synthesize and secrete BDNF and are targets for antidepressant treatments (Autry and Monteggia, ; Bjorkholm and Monteggia, ; Hisaoka‐Nakashima et al, ). Several recent studies have shown that the SSRI antidepressants fluoxetine and paroxetine and the TCAs imipramine and amitriptyline upregulate the BDNF mRNA levels in primary cortical astrocyte cultures, but not in neuronal cultures, in a monoamine‐independent manner (Allaman, Fiumelli, Magistretti, & Martin, ; Hisaoka‐Nakashima et al ; Kittel‐Schneider et al, ; Musazzi et al, ; Takano, Yamasaki, Kawabe, Moriyama, & Nakamura, ), possibly through a direct effect on the ERK‐ and p38 MAPK‐dependent signaling pathway. Moreover, overexpression of BDNF in hippocampal astrocytes in vivo produced anxiolytic‐ and antidepressant‐like effects either alone or in combination with fluoxetine (Quesseveur et al, ).…”

Orcinol glucoside produces antidepressant effects by blocking the behavioural and neuronal deficits caused by chronic stress

“…Chronic stress and glucocorticoid administration may induce depressive effects in rats by lowering hippocampal BDNF levels (Smith et al, 1995;Hansson et al, 2003), whereas some antidepressants are reported to achieve their efficacy by increasing BDNF in the hippocampus (Li et al, 2011;Takano et al, 2012;Zhang et al, 2012). Although the underlying mechanisms remain unidentified, it has been reported that glucocorticoids can prevent synaptic function maturation through suppression of the BDNF-stimulated MAPK/ERK pathway (Kumamaru et al, 2011(Kumamaru et al, , 2008.…”