PAI-1 protein is a key molecular effector in the transition from normal to PTSD-like fear memory

C Bouarab (1) , V Roullot-Lacarrière (1) , M Vallée (1) , A Le Roux (1) , C Guette (1) , M Mennesson (1) , A Marighetto (1) , A Desmedt (1) , P V Piazza (1) , J M Revest (1)

1 U1215 Inserm - UB - Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale

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.

Domaines: Sciences du Vivant [q-bio]

C Bouarab, V Roullot-Lacarrière, M Vallée, A Le Roux, C Guette, et al.. PAI-1 protein is a key molecular effector in the transition from normal to PTSD-like fear memory. Molecular Psychiatry, 2021, ⟨10.1038/s41380-021-01024-1⟩. ⟨hal-03424451⟩