Journal
MOLECULAR PSYCHIATRY
Volume 26, Issue 9, Pages 4968-4981Publisher
SPRINGERNATURE
DOI: 10.1038/s41380-021-01024-1
Keywords
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Funding
- Magendie Neurocentre
- Biochemistry and Biophysics Facility of the Bordeaux Neurocampus - LABEX BRAIN [ANR-10-LABX-43]
- INSERM [U121519G]
- Agence Nationale pour la Recherche [ANR-14-CE13-0026-01]
- Aquitaine Regional Council
- University of Bordeaux
- Agence Nationale de la Recherche (ANR) [ANR-14-CE13-0026] Funding Source: Agence Nationale de la Recherche (ANR)
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Moderate stress can enhance memory while intense stress may lead to pathological memories, with the transition being attributed to the balance between tPA and PAI-1 protein expression.
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.
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