Department of integrative medicine and neurobiology, Shanghai medical college, Fudan University, Shanghai 200032, PR China.
J Affect Disord. 2012 Dec 10;141(2-3):367-72. doi: 10.1016/j.jad.2012.03.018. Epub 2012 Jun 1.
Because there is evidence that certain neurotrophic factors are involved in depression and the mechanism of antidepressant treatment, it is hypothesized that neurotrophic factors may also play a functional role in the etiology of depression and treatment. Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor (TGF-β)-super-family. We performed a study to assess the impact of chronic unpredictable stress (CUS) and clomipramine treatment on GDNF expression in the rat hippocampus.
Using a rat model of CUS-induced depression, we administered clomipramine, one of the typical antidepressants, every day for 3 weeks starting 2 weeks after the beginning of the experiment. GDNF level in the hippocampus was detected by immunohistochemsitry, Western blot analysis, and reverse transcription-polymerase chain reaction (RT-PCR). Behavioral changes were measured by forced swimming test (FST) and open field test (OFT).
Animals exposed to CUS showed depression-like behavior and exhibited a significant decrease in GDNF expression in the hippocampus. Chronic clomipramine treatment reversed the behavioral deficits and the decrease in GDNF levels induced by CUS.
The relatively small number of the depression-model rats may cause some bias of behavioral tests.
In our study, chronic clomipramine treatment restored GDNF expression in the hippocampus of CUS-induced depression rats, suggesting that GDNF is involved in the behavioral responses to antidepressants. The beneficial effects of clomipramine suggest that GDNF may be a viable target for new antidepressant drug development.
有证据表明，某些神经营养因子与抑郁症有关，以及抗抑郁治疗的机制，因此假设神经营养因子也可能在抑郁症的发病机制和治疗中发挥功能作用。胶质细胞源性神经营养因子（GDNF）是转化生长因子（TGF-β）超家族的一员。我们进行了一项研究，评估慢性不可预测性应激（CUS）和氯米帕明治疗对大鼠海马 GDNF 表达的影响。
使用 CUS 诱导的抑郁大鼠模型，我们从实验开始后 2 周开始每天给予氯米帕明（一种典型的抗抑郁药），持续 3 周。通过免疫组织化学、Western blot 分析和逆转录聚合酶链反应（RT-PCR）检测海马中的 GDNF 水平。通过强迫游泳试验（FST）和旷场试验（OFT）测量行为变化。
暴露于 CUS 的动物表现出抑郁样行为，并表现出海马 GDNF 表达显著降低。慢性氯米帕明治疗逆转了 CUS 诱导的行为缺陷和 GDNF 水平降低。
抑郁模型大鼠的数量相对较少，可能会导致行为测试存在一些偏差。
在我们的研究中，慢性氯米帕明治疗恢复了 CUS 诱导的抑郁大鼠海马中的 GDNF 表达，表明 GDNF 参与了抗抑郁药的行为反应。氯米帕明的有益作用表明 GDNF 可能是新的抗抑郁药物开发的一个可行靶点。
