The Effect of Histone Deacetylase Inhibitor on the Expression Level of Glucococrticoid Receptor in Rat Forebrain under Hypoxia

Abstract

The activity of the gene transcription depends to a large extent on the histone acetylation status and can be affected by different stimuli such as hypoxia. Histone deacetylase inhibitors promote gene transcription by facilitating histone acetylation and are thus considered as candidates for target therapy of posthypoxic states. In the present study, using immunohistochemistry, the effect of the histone deacetylase inhibitor trihostatin A (TSA) on the expression level of glucocorticoid receptor (GR) have been analyzed in the neocortex and hippocampus of rats in an original model of severe hypobaric hypoxia (SHH). It has been found that injections of TSA in rats facilitated GR expression after SHH in the neocortex and CA1 field but not in the dentate girus of hippocampus. GR overexpression enhances the toxicity of circulating glucocorticoid hormones on the hippocampal neurons. Stimulation of GR expression by TSA injections in the CA1 field of the hippocampus may lead to maladaptation, making possible damaging effects of unfavorable factors, such as hypoxia. The data obtained indicate that therapy using histone deacetylase inhibitors may have adverse side effects for vulnerable brain neurons.