The aim of the study was to assess the possible role of hypoxia-inducible factor HIF-1 in the mechanisms of formation of post-stress depression and the antidepressant effect of intermittent remote limb ischemic conditioning (RIC) in rats. It was shown that the formation of experimental depression in the “learned helplessness” model is characterized by a two-wave profile of stress-induced expression of the regulatory alpha subunit of the HIF-1 factor (HIF-1α) in the hippocampus and neocortex of rats, including not only the early peak (on the 1st day), but also the late one (on the 10th day). Postconditioning with RIC, which prevents the formation of a depressive-like state, increased the early expression of HIF-1α and neutralized the late expression. Inhibition of stress-induced expression of HIF-1α by administration of the blocking inhibitor topotecan did not affect the formation of a depressive-like state. However, administration of topotecan before RIC preconditioning, blocking the early wave of HIF-1α, completely neutralized its preventive antidepressant effect. Thus, the induction of HIF-1α observed in the “learned helplessness” model does not play a pathogenetic role, but the early induction of HIF-1α in response to RIC is necessary for the implementation of its antidepressant effect.
Баранова et al. (Sun,) studied this question.