Amitriptyline induces brain-derived neurotrophic factor (BDNF) mRNA expression through ERK-dependent modulation of multiple BDNF mRNA variants in primary cultured rat cortical astrocytes and microglia

Brain Research
Kazue Hisaoka-NakashimaYoshihiro Nakata

Abstract

A significant role of brain-derived neurotrophic factor (BDNF) has been previously implicated in the therapeutic effect of antidepressants. To ascertain the contribution of specific cell types in the brain that produce BDNF following antidepressant treatment, the effects of the tricyclic antidepressant amitriptyline on rat primary neuronal, astrocytic and microglial cortical cultures were examined. Amitriptyline increased the expression of BDNF mRNA in astrocytic and microglial cultures but not neuronal cultures. Antidepressants with distinct mechanisms of action, such as clomipramine, duloxetine and fluvoxamine, also increased BDNF mRNA expression in astrocytic and microglial cultures. There are multiple BDNF mRNA variants (exon I, IIA, IV and VI) expressed in astrocytes and microglia and the variant induced by antidepressants has yet to be elaborated. Treatment with antidepressants increased the expression of exon I, IV and VI in astrocyte and microglia. Clomipramine alone significantly upregulated expression of exon IIA. The amitriptyline-induced expression of both total and individual BDNF mRNA variants (exon I, IV and VI) were blocked by MEK inhibitor U0126, indicating MEK/ERK signaling is required in the expression of BDN...Continue Reading

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Citations

Mar 21, 2017·Glia·Qian WangTian-Ming Gao
Mar 25, 2017·The International Journal of Neuropsychopharmacology·Feng-Guo LiuChao Huang
Sep 1, 2020·Cancer Investigation·F Lavergne, T M Jay
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May 29, 2020·Neuropharmacology·Matjaž StenovecRobert Zorec
Jun 12, 2018·EBioMedicine·Manao KinoshitaSchuichi Koizumi

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