Dysregulation of Protein Kinase C in Adult Depression and Suicide: Evidence From Postmortem Brain Studies

• Published in: The international journal of neuropsychopharmacology 2021-05, Vol.24 (5), p.400-408
• Main Authors: Pandey, Ghanshyam N, Sharma, Anuradha, Rizavi, Hooriyah S, Ren, Xinguo
• Format: Article
• Language: English
• Subjects: Adult; Autopsy; Brain research; Depression, Mental; Depressive Disorder, Major - enzymology; Development and progression; Female; Health aspects; Humans; Isoenzymes; Isoenzymes - metabolism; Male; Middle Aged; Physiological aspects; Prefrontal Cortex - enzymology; Protein biosynthesis; Protein Kinase C - metabolism; Protein kinases; Regular s; RNA, Messenger - metabolism; Suicidal behavior; Suicide, Completed; Young Adult
• ISSN: 1461-1457; 1469-5111
• DOI: 10.1093/ijnp/pyab003

Abstract Background Several lines of evidence suggest the abnormalities of protein kinase C (PKC) signaling system in mood disorders and suicide based primarily on the studies of PKC and its isozymes in the platelets and postmortem brain of depressed and suicidal subjects. In this study, we examined the role of PKC isozymes in depression and suicide. Methods We determined the protein and mRNA expression of various PKC isozymes in the prefrontal cortical region (Brodmann area 9) in 24 normal control subjects, 24 depressed suicide (DS) subjects, and 12 depressed nonsuicide (DNS) subjects. The levels of mRNA in the prefrontal cortex were determined by quantitative real-time reverse transcription PCR, and the protein expression was determined by western blotting. Results We observed a significant decrease in mRNA expression of PKCα, PKCβI, PKCδ, and PKCε and decreased protein expression in either the membrane or the cytosol fraction of PKC isozymes PKCα, PKCβI, PKCβII, and PKCδ in DS and DNS subjects compared with normal control subjects. Conclusions The current study provides detailed evidence of specific dysregulation of certain PKC isozymes in the postmortem brain of DS and DNS subjects and further supports earlier evidence for the role of PKC in the platelets and brain of the adult and teenage depressed and suicidal population. This comprehensive study may lead to further knowledge of the involvement of PKC in the pathophysiology of depression and suicide.