FADD adaptor and PEA-15/ERK1/2 partners in major depression and schizophrenia postmortem brains: Basal contents and effects of psychotropic treatments.

Détails

ID Serval
serval:BIB_DA022E25E7EF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
FADD adaptor and PEA-15/ERK1/2 partners in major depression and schizophrenia postmortem brains: Basal contents and effects of psychotropic treatments.
Périodique
Neuroscience
Auteur(s)
García-Fuster M.J., Díez-Alarcia R., Ferrer-Alcón M., La Harpe R., Meana J.J., García-Sevilla J.A.
ISSN
1873-7544 (Electronic)
ISSN-L
0306-4522
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
277
Pages
541-551
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish
Résumé
Enhanced brain apoptosis (neurons and glia) may be involved in major depression (MD) and schizophrenia (SZ), mainly through the activation of the intrinsic (mitochondrial) apoptotic pathway. In the extrinsic death pathway, pro-apoptotic Fas-associated death domain (FADD) adaptor and its non-apoptotic p-Ser194 FADD form have critical roles interacting with other death regulators such as phosphoprotein enriched in astrocytes of 15kDa (PEA-15) and extracellular signal-regulated kinase (ERK). The basal status of FADD (protein and messenger RNA (mRNA)) and the effects of psychotropic drugs (detected in blood/urine samples) were first assessed in postmortem prefrontal cortex of MD and SZ subjects (including a non-MD/SZ suicide group). In MD, p-FADD, but not total FADD (and mRNA), was increased (26%, n=24; all MD subjects) as well as p-FADD/FADD ratio (a pro-survival marker) in antidepressant-free MD subjects (50%, n=10). In contrast, cortical FADD (and mRNA), p-FADD, and p-FADD/FADD were not altered in SZ brains (n=21) regardless of antipsychotic medications (except enhanced mRNA in treated subjects). Similar negative results were quantified in the non-MD/SZ suicide group. In MD, the regulation of multifunctional PEA-15 (i.e., p-Ser116 PEA-15 blocks pro-apoptotic FADD and PEA-15 prevents pro-survival ERK action) and the modulation of p-ERK1/2 were also investigated. Cortical p-PEA-15 was not changed whereas PEA-15 was increased mainly in antidepressant-treated subjects (16-20%). Interestingly, cortical p-ERK1/2/ERK1/2 ratio was reduced (33%) in antidepressant-free when compared to antidepressant-treated MD subjects. The neurochemical adaptations of brain FADD (increased p-FADD and pro-survival p-FADD/FADD ratio), as well as its interaction with PEA-15, could play a major role to counteract the known activation of the mitochondrial apoptotic pathway in MD.
Pubmed
Web of science
Création de la notice
27/10/2014 16:58
Dernière modification de la notice
03/03/2018 21:54
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