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

Autor: Rafael Fernandez, Nader Perroud, Eladia Ballmann, Alain Malafosse, Romano La Harpe, Félicien Karege, S. Burkhardt
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Adult
Male
medicine.medical_specialty
PTEN Phosphohydrolase/metabolism
Prefrontal Cortex
Prefrontal Cortex/enzymology
03 medical and health sciences
ddc:616.89
0302 clinical medicine
GSK-3
Neurotrophic factors
Internal medicine
ddc:570
medicine
Proto-Oncogene Proteins c-akt/metabolism
PTEN
Humans
Kinase activity
Phosphorylation
Prefrontal cortex
Protein kinase B
Depressive Disorder
Major/complications/enzymology

Suicide/psychology
Biological Psychiatry
PI3K/AKT/mTOR pathway
030304 developmental biology
ddc:613
Depressive Disorder
Major

0303 health sciences
biology
ddc:614.1
PTEN Phosphohydrolase
Middle Aged
16. Peace & justice
Suicide
Psychiatry and Mental health
Kinetics
Neuropsychology and Physiological Psychology
Endocrinology
biology.protein
Female
Phosphatidylinositol 3-Kinase
Psychology
Proto-Oncogene Proteins c-akt
Phosphatidylinositol 3-Kinase/metabolism
030217 neurology & neurosurgery
Zdroj: Neuropsychobiology, Vol. 63, No 4 (2011) pp. 224-31
ISSN: 0302-282X
Popis: 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.
Databáze: OpenAIRE