PAI-1 protein is a key molecular effector in the transition from normal to PTSD-like fear memory
Chloé Bouarab, Valérie Roullot-Lacarrière, Monique Vallée, A Le Roux, Christelle Guette, Marie Mennesson, Aline Marighetto, Aline Desmedt, Pier Vincenzo Piazza, Jean‐Michel Revest
Abstract
Abstract Moderate stress increases memory and facilitates adaptation. In contrast, intense stress can induce pathological memories as observed in post-traumatic stress disorders (PTSD). A shift in the balance between the expression of tPA and PAI-1 proteins is responsible for this transition. In conditions of moderate stress, glucocorticoid hormones increase the expression of the tPA protein in the hippocampal brain region which by triggering the Erk1/2 MAPK signaling cascade strengthens memory. When stress is particularly intense, very high levels of glucocorticoid hormones then increase the production of PAI-1 protein, which by blocking the activity of tPA induces PTSD-like memories. PAI-1 levels after trauma could be a predictive biomarker of the subsequent appearance of PTSD and pharmacological inhibition of PAI-1 activity a new therapeutic approach to this debilitating condition.