BACKGROUND: 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. METHOD: 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). RESULTS: 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. LIMITATION: The relatively small number of the depression-model rats may cause some bias of behavioral tests. CONCLUSION: 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.
BACKGROUND: 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. METHOD: 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). RESULTS: 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. LIMITATION: The relatively small number of the depression-model rats may cause some bias of behavioral tests. CONCLUSION: In our study, chronic clomipramine treatment restored GDNF expression in the hippocampus of CUS-induced depressionrats, 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.
Authors: Kr Roversi; Caren Tatiane de David Antoniazzi; L H Milanesi; H Z Rosa; M Kronbauer; D R Rossato; T Duarte; M M Duarte; Marilise E Burger Journal: Mol Neurobiol Date: 2019-02-11 Impact factor: 5.590
Authors: Daniela D Leffa; Samira S Valvassori; Roger B Varela; Jésica Lopes-Borges; Francine Daumann; Luiza M Longaretti; Ana Luiza F Dajori; João Quevedo; Vanessa M Andrade Journal: Metab Brain Dis Date: 2015-05-22 Impact factor: 3.584
Authors: Ajaykumar N Sharma; Bruno Fernando Borges da Costa e Silva; Jair C Soares; André F Carvalho; Joao Quevedo Journal: J Affect Disord Date: 2016-03-02 Impact factor: 4.839