Alteration in kinase activity but not in protein levels of protein kinase B and glycogen synthase kinase-3 beta in ventral prefrontal cortex of depressed suicide victims

作者：Karege Felicien^*; Perroud Nader; Burkhardt Sandra; Schwald Michele; Ballmann Eladia; La Harpe Romano; Malafosse Alain

来源：Biological Psychiatry, 2007, 61(2): 240-245.

DOI：10.1016/j.biopsych.2006.04.036

• Akt
• GSK-3 alpha/beta
• suicide
• postmortem prefrontal cortex
• major depression disorder

Background: Past studies in the neurobiology of suicide bave reported alterations in serotonin and downstream effectors, such as Akt/protein kinase B. In this study, we aimed to examine possible abnormality in the Akt/glycogen syntbase kinase-3 beta (GSK-3 beta) axis of depressed suicide victims' brains.
Methods: Twenty suicide victims and 20 drug-free non-suicide subjects were included for a postmortem study. The ventral prefrontal cortex area (BA'11) was used, and antemortem diagnoses of major depression disorder (MDD) (DSM-IV) were made from Institution's records. The protein levels of GSK-3 alpha/beta and Akt-1 were assayed with the Western blot method, and the kinase activity of Akt and GSK-3 alpha/beta were determined by phospborylation of specific substrates.
Results: There was no change either in GSK-3 alpha/beta and Akt-1 protein levels or in litbium-inbibitable total GSK-3 alpha/beta enzyme activity of the ventral prefrontal cortex. The enzyme activitiy of Akt decreased significantly [analysis of valiance (ANOVA): F6,36) = 5.372; p =.003], whereas GSK-3 beta activity increased significantly [ANOVA. F(3,36) = 8.567; p =.002] in depressed suicide victims and non-suicide subjects but not in non-depressed suicide victims,
Conclusions: This study indicated that the activity rather than the protein levels of Akt and GSK-3 beta was altered. The alteration was associated with MDD rather than with suicide per se.

• 出版日期2007-1-15