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 |
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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 |
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