Fig. 6. Schematic model of glucocorticoid (GC)-induced molecular mechanism mediating the shift from adaptive to PTSD-like memory.
Under traumatic conditions, high levels of GC [1] induce the expression of PAI-1 [2] that by inhibiting tPA blocks the proteolytic processing of pro-BDNF in mature BDNF [3] by plasmin. The resulting consecutive blockade of TrkB/Erk1/2MAPK activation [4] leads to impairment of hippocampal function, which thereby promotes the formation of a decontextualized (cue based) traumatic memory [5]. By lowering hippocampal PAI-1 activity, tiplaxtinin [6] restores the activity of this molecular cascade, promotes the formation of a hippocampal-dependent adaptive (“contextualized”) fear memory and thus normalizes traumatic memory. This model, based on several studies including our own, is discussed in the main text.