The dynamics of HIF-1α expression in the rat brain at different stages of experimental posttraumatic stress disorder and its correction with moderate hypoxia

Abstract

The dynamics of the expression of the HIF factor-1 α-subunit, which is related to products of early genes, has been studied in the neocortex, the hippocampus, and the hypothalamus of rats during the development of posttraumatic stress disorder (PTSD) in a stress–restress model and using triple moderate hypobaric hypoxia (MH3), which prevents the formation of this anxiety pathology. The immunohistochemical method has shown that after pathogenic traumatic stress (TS), during the primary (“hidden”) period of modeled PTSD formation, the level of HIF-1α expression did not change significantly; however, after restress it rapidly increased in all regions of the brain. An increased expression of this factor remained in animals with experimental PTSD for up to 10 days after restress. Exposure to MH3 before TS or before restress compensated for these disturbances: fully in the hippocampus and partly in the neocortex; it inhibited the prolonged over-induction of the HIF-1α, which may be one of the mechanisms that mediate an anxiolytic effect of hypoxia. Along with this, preconditioning with MH3 significantly decreased the content of HIF-1α after TS, thus preventing activation of the HIF-1 factor during the hidden period, which is likely associated with the formation of pathological reactivity to restress. These facts indicate the pathogenetic role of HIF-1 in certain periods of experimental PTSD and the correcting effect of hypoxic preconditioning.