Effect of cholestasis and NeuroAid treatment on the expression of Bax, Bcl-2, Pgc-1α and Tfam genes involved in apoptosis and mitochondrial biogenesis in the striatum of male rats.

ABSTRACT

Cholestasis means impaired bile synthesis or secretion. In fact, it is a bile flow reduction following Bile Duct Ligation (BDL). Cholestasis has a main role in necrosis and apoptosis. Apoptosis is a form of programmed cell death that has intrinsic and extrinsic pathways. The intrinsic pathway is mediated by Bcl-2 (B cell lymphoma-2) proteins which integrate death and survival signals. Bcl-2 has anti-apoptotic and Bax has pro-apoptotic effects. Also, striatum is one of the brain regions that has high expressions of Bcl-2 proteins. Moreover, Tfam and Pgc-1α are involved in mitochondrial biogenesis. On the other hand, NeuroAid, is a drug that has neuroprotective and anti-apoptosis effects. In this study, using quantitative PCR, we measured the expression of all these genes in the striatum of male rats following BDL and NeuroAid administration. Results showed, BDL increased the expression of Bax and Tfam and decreased the expression of Bcl-2. NeuroAid restored the effect of BDL on the expression of Bax, while did not alter the effect of BDL on Bcl-2. In addition, it increased the expression of Tfam that was previously elevated by BDL and raised the expression of Tfam in normal rats. Both BDL and NeuroAid, had no effect on Pgc-1α. In conclusion, cholestasis increased the expression of Bax and decreased the expression of Bcl-2, and this effect may have related to enhanced susceptibility of mitochondrial pathways following oxidative stress. Tfam expression was increased following cholestasis and this effect may have related to cellular compensatory mechanisms against high accumulation of free radicals or mitochondrial biogenesis failure. Furthermore, NeuroAid may play a role against apoptosis and can be used to increase mitochondrial biogenesis.