Alterations in phosphatidylinositol 3-kinase activity and PTEN phosphatase in the prefrontal cortex of depressed suicide victims.

Détails

ID Serval
serval:BIB_476148A24526
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Alterations in phosphatidylinositol 3-kinase activity and PTEN phosphatase in the prefrontal cortex of depressed suicide victims.
Périodique
Neuropsychobiology
Auteur(s)
Karege F., Perroud N., Burkhardt S., Fernandez R., Ballmann E., La Harpe R., Malafosse A.
ISSN
1423-0224 (Electronic)
ISSN-L
0302-282X
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
63
Numéro
4
Pages
224-231
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
BACKGROUND: Recent studies have reported alterations in protein kinase B (PKB)/Akt and in its downstream target, glycogen synthase kinase 3β, in depression and suicide. The aim of the present study was to investigate possible impairment of the upstream regulators, namely phosphatidylinositol 3-kinase (PI3K) and PTEN.
METHODS: The ventral prefrontal cortex (Brodmann's area 11) of 24 suicide victims and 24 drug-free nonsuicide subjects was used. The antemortem diagnoses of major depression disorder were obtained from the institutional records or psychological autopsy, and toxicological analyses were performed. Protein levels of PI3K and PTEN were assayed using the immunoblot method, and the kinase activity of PI3K and Akt was determined by phosphorylation of specific substrates.
RESULTS: A decrease was observed in the enzymatic activity of PI3K [ANOVA: F(3, 44) = 9.20; p < 0.001] and Akt1 [ANOVA: F(3, 44) = 13.59; p < 0.001], without any change in protein levels, in both depressed suicide victims and depressed nonsuicide subjects (p < 0.01 and p < 0.002, respectively). PTEN protein levels were increased in the same groups [ANOVA: F(3, 44) = 10.5; p < 0.001]. No change was observed in nondepressed suicide victims.
CONCLUSION: This study concludes that attenuation of kinase activity of PKB/Akt in depressed suicide victims may be due to the combined dysregulation of PTEN and PI3K resulting in insufficient phosphorylation of lipid second messengers. The effect is associated with major depression rather than with suicide per se. Given the cellular deficits reported in major depression, the study of enzymes involved in cell survival and neuroplasticity is particularly relevant to neurotrophic factor dysregulation in depression.
Mots-clé
Adult, Depressive Disorder, Major/complications, Depressive Disorder, Major/enzymology, Female, Humans, Kinetics, Male, Middle Aged, PTEN Phosphohydrolase/metabolism, Phosphatidylinositol 3-Kinase/metabolism, Phosphorylation, Prefrontal Cortex/enzymology, Proto-Oncogene Proteins c-akt/metabolism, Suicide/psychology
Pubmed
Web of science
Création de la notice
09/02/2015 14:05
Dernière modification de la notice
03/03/2018 16:50
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