Abstract
Purpose: To investigate the influence of trichostatin A on nerve cell apoptosis in depressive rats and to explore the probable molecular mechanism of action.Methods: A total of 36 Sprague-Dawley rats weighing 200 - 220 g were divided into sham group (n = 12), model group (n = 12) and trichostatin group (n = 12) by randomization. The protein expressions of phosphorylated cAMP responsive element-binding protein (p-CREB) and BDNF, as well as the mRNA expression levels of B-cell lymphoma-2 (Bcl-2) and caspase-3 in each group of rat hippocampus were determined by Western blotting and quantitative reverse transcription-polymerase chain reaction (qRTPCR), respectively. The apoptosis of nerve cells in the brain tissues of the rats was labeled using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining.Results: Compared with those in the sham group, the degree of sucrose preference decreased markedly, while the immobility time after forced swimming test was extended, and the relative expression levels of p-CREB and BDNF proteins in the hippocampus declined (p < 0.05). The mRNA levels of Bcl-2 and caspase-3 and cell apoptosis rate were increased in the model group (p < 0.05). In comparison with the model group, the trichostatin group exhibited increased sucrose preference degree, shortened immobility time following a forced swimming test, and elevated relative expression levels p-CREB and BDNF proteins in the hippocampus (p < 0.05), but lowered mRNA levels of Bcl-2 and caspase-3 and cell apoptosis rate, displaying statistically significant differences (p < 0.05).Conclusion: Trichostatin A reduces cell apoptosis and ameliorates the depression-like behaviors of rats via the regulation of CREB/BDNF signaling pathway. These findings provide new insights into Trichostatin A for the management of depression.
Highlights
Depression, one of the leading causes of disability in the world, is characterized by selfdefiance, divergent thinking, low spirits [1]
As an inhibitor of Histone deacetylases (HDACs), trichostatin A may become a promising tool for the treatment of depression
Inducing acetylation in the hippocampus by trichostatin A can distinctly enhance the preference for sucrose and reduce the immobility time in forced swimming test of the depressive rats [7]
Summary
Depression, one of the leading causes of disability in the world, is characterized by selfdefiance, divergent thinking, low spirits [1]. About one-sixth of people die of depression, aggravating the social medical burden around the globe and posing a greater threat to the quality of life of patients with cardiovascular disease [2]. Histone deacetylases (HDACs) are capable of regulating chromatin function by means of histone acetylation and play crucial roles in learning, memory and synaptic plasticity [4]. In the culture of cortical neurons of mice, inhibiting HDAC6 via genetic and pharmacologic approaches can maintain the survival and regeneration of neurons under the condition of oxidative stress. In the rat model of chronic depression induced by social pressure, the expression of HDAC5 is raised in the prefrontal cortex [5], while trichostatin A, as a HDAC inhibitor, can improve the depressive behavior [6,7]
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