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

C. Bouarab, V. Roullot-Lacarrière, M. Vallée, A. Le Roux, C. Guette, M. Mennesson, A. Marighetto, A. Desmedt, P. V. Piazza, J. M. Revest
Mol Psychiatry. 2021-01-28; :
DOI: 10.1038/s41380-021-01024-1

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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.

Auteurs Bordeaux Neurocampus