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

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

1 INSERM - Institut National de la Santé et de la Recherche Médicale

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 Erk1/2MAPK 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.

Domains: Life Sciences [q-bio]

C. Bouarab, V. Roullot-Lacarrière, M. Vallee, 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-03132810⟩