Targeting the brain under stress : selective glucocorticoid receptor modulation

Abstract

In this thesis studies are reported aimed to modulate the function of the GR by targeting GR-coregulator interactions. To achieve this goal, we used two different approaches. Firstly, we manipulated the splicing of SRC-1 with antisense oligonucleotides (AONs) administered in the CeA to change the relative expression of the two SRC-1 splice variants. Secondly, we used two novel GR ligands that allowed certain GR-coregulator interactions while preventing others, thus resulting in a mixed GR-coregulator interaction profile, which exhibited a spectrum of both agonist and antagonist activities