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C.-H. Peng, S.-H. Chiou, C.-K. Cheng; Imipramine Against Lipopolysaccharide-Induced Apoptosis in Retinal Stem Cells Mediated by Activation of BDNF Pathway. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5154.
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Depression is accompanied by the activation of the inflammatory-response system, and increased production of proinflammatory cytokines may play a role in the pathophysiology of depressive disorders. Imipramine (IM), a tricyclic antidepressant drug, has recently been shown to promote neurogenesis. However, whether IM elicits a neuroprotective or anti-inflammatory effect, or promotes the differentiation of retinal stem cells (RSCs) remains to be elucidated.
We cultured RSCs derived from the adult rats as an in vitro model to evaluate the RSCs drug-modulation effects of IM.
Our results showed that IM treatment significantly increased the proliferation rate of RSCs, and up-regulated the mRNA and protein expression of BDNF in Day-7 IM-treated RSCs. Similar to BDNF-treated effect, incubation of RSCs with IM increased Bcl-2 protein levels and further prevented lipopolysaccharide (LPS)-induced apoptosis. Inhibition of BDNF expression with small interfering RNA (siRNA) significantly decreased Bcl-2 protein levels and abrogated the neuroprotective effects of IM against LPS-induced apoptosis in IM-treated RSCs. Moreover, using microdialysis with high performance liquid chromatography -electrochemical detection (HPLC-ED), the functional release of serotonin in the process of serotoninergic differentiation of IM-treated RSCs was concomitantly increasing and was mediated by the activation of the BDNF pathway/Bcl-2 cascades.
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