EN
Apoptosis is controlled by the balance between pro- (Bax) and anti-(Bcl-2, Bcl-xl) apoptotic proteins within the cell. Bcl-2 and Bcl-xl interact with Bax in the outer mitochondrial membrane and regulate the release of cytochrome c, which activates caspases, the main executors of apoptosis. The increased ratio of pro- vs. antiapoptotic proteins is associated with an enhanced vulnerability to apoptotic activation. The chronic mild stress (CMS) procedure induces depression-like symptoms in animals. The rats subjected for a prolonged period of time to a variety of mild stressors gradually decrease their responsiveness to rewarding stimuli (e.g., consumption of sweet pellets). We aimed to investigate the expression of Bcl-2, Bcl-xl and Bax mRNAs in the thalamus of rats subjected to the 3-weeks CMS. Three groups of male Wistar rats, selected basing on behavioral test of sucrose (1% solution) consumption – sham, stress reactive and stress non-reactive, were considered. The mRNA expression was measured by quantitative RT-PCR applying TaqMan probes. We found that in the thalamus of rats developing anhedonia to sucrose consumption after the CMS, the mRNA expression of both anti-apoptotic (Bcl-2 and Bcl-xl) and pro-apoptotic (Bax) genes was significantly attenuated, though to a various extent. In the stress reactive animals, the Bcl-2 mRNA was decreased by 57% (p<0.01), Bcl-xl – by 51% (p<0.05) and Bax – by 24% (p<0.05), while no change was noticed in the stress non-reactive animals. Further analysis revealed a significant decrease in the Bcl-2/Bax and Bcl-xl/Bax ratios (respectively, by 48% and 25%; p<0.01) in the stress reactive animals, and no change in case of the stress non-reactive animals. Our results suggest that the behavioral reactiveness of rats to the CMS is associated with the enhanced susceptibility to apoptotic activation and development of apoptotic processes in the thalamus. Supported by statutory funds of the Institute of Pharmacology, PAS.