Desipramine Activated Bcl-2 Expression and Inhibited Lipopolysaccharide-Induced Apoptosis in Hippocampus-Derived Adult Neural Stem Cells

Journal of Pharmacological Sciences

Yuh-Lih Chang²  Kwok-Han Chan⁴  Shih-Jen Chen³  Wen-Ming Hsu³  Yi-Ping Yang²  Yu-Yin Huang⁴  Chi-Hsien Peng³  Hsiao-Jung Wang²  Yi-Pen Chou¹  Chih-Chiau Wu³ 

[1] Department of Anesthesiology, Cheng-Hsin Rehabilitation Medical Center, Taiwan;Department of Pharmacy, Taipei Veterans General Hospital and National Yang-Ming University, Taiwan;Department of Ophthalmology, Taipei Veterans General Hospital and National Yang-Ming University, Taiwan;Department of Anesthesiology, Taipei Veterans General Hospital and National Yang-Ming University, Taiwan

关键词: desipramine;    neural stem cell;    real-time RT-PCR;    small interfering RNA (siRNA);   

DOI  :  10.1254/jphs.FP0061255

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(46)Cited-By(32)Desipramine (DP) is a tricyclic antidepressant used for treating depression and numerous other psychiatric disorders. Recent studies have shown that DP can promote neurogenesis and improve the survival rate of hippocampal neurons. However, whether DP induces neuroprotection or promotes the differentiation of neural stem cells (NSCs) needs to be elucidated. In this study, we cultured NSCs derived from the hippocampal tissues of adult rats as an in vitro model to evaluate the modulation effect of DP on NSCs. First, we demonstrated that the expression of Bcl-2 mRNA and nestin in 2 μM DP-treated NSCs were up-regulated and detected by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The results of Western blotting and immunofluorescent study confirmed that Bcl-2 protein expression was significantly increased in Day 3 DP-treated NSCs. Using the Bcl-2 small interfering RNA (siRNA) method, our results further showed that DP protects the lipopolysaccharide (LPS)-induced apoptosis in NSCs, in part by activating the expression of Bcl-2. Furthermore, DP treatment significantly inhibited the induction of proinflammatory factor interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the culture medium of LPS-treated NSCs mediated by Bcl-2 modulation. The results of high performance liquid chromatography coupled to electrochemical detection further confirmed that DP significantly increased the functional production of serotonin (26 ± 3.5 μM, DP-treated 96 h) and noradrenaline (50 ± 8.9 μM, DP-treated 96 h) in NSCs through activation of the MAPK/ERK pathway and partially mediated by Bcl-2. In conclusion, the present results indicate that DP can increase neuroprotection ability by inhibiting the LPS-induced inflammatory process in NSCs via the modulation of Bcl-2 expression, as confirmed by the siRNA method.

【 授权许可】

Unknown