Reduced activation and expression of ERK1/2 MAP kinase in the post‐mortem brain of depressed suicide subjects

• Published in: Journal of neurochemistry Vol. 77; no. 3; pp. 916 - 928
• Main Authors: Dwivedi, Y., Rizavi, H. S., Roberts, R. C., Conley, R. C., Tamminga, C. A., Pandey, G. N.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.05.2001; Blackwell
• Subjects: 44 MAP kinases; Adult; Adult and adolescent clinical studies; Aged; Biological and medical sciences; Brain - enzymology; Cell Membrane - enzymology; Cell Nucleus - enzymology; Cytosol - enzymology; Depression; Depression - enzymology; Dual-Specificity Phosphatases; Enzyme Activation; ERK1; extracellular signal-regulated kinase; Female; Gene Expression; Hippocampus - enzymology; human post‐mortem brain; Humans; Male; Medical sciences; Middle Aged; Mitogen-Activated Protein Kinase 1 - analysis; Mitogen-Activated Protein Kinase 1 - genetics; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinase Phosphatases; Mitogen-Activated Protein Kinases - analysis; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; MKP2; Mood disorders; p42; Phosphorylation; Prefrontal Cortex - enzymology; Protein Tyrosine Phosphatases - analysis; Protein Tyrosine Phosphatases - metabolism; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; RNA, Messenger - analysis; Suicide; Mood disorder; Human; Enzymatic activity; Postmortem; Depression; Gene expression; Suicide; Brain (vertebrata)
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2001.00300.x

The extracellular regulated kinases (ERK) 1 and ERK2 are members of mitogen‐activated protein (MAP) kinase family that play an important role in transducing extracellular signals to the nucleus and have been implicated in a broad spectrum of biological responses. To test the hypothesis that MAP kinases may be involved in depression, we examined the activation of p44/42 MAP kinase and expression of ERK1 and ERK2 in the post‐mortem brain tissue obtained from non‐psychiatric control subjects (n = 11) and age‐ and the post‐mortem interval‐matched depressed suicide subjects (n = 11). We observed that p44/42 MAP kinase activity was significantly decreased in the prefrontal cortical areas (Brodmann's areas 8, 9 and 10) and the hippocampus of depressed suicide subjects without any change in the cerebellum. This decrease was associated with a decrease in mRNA and protein levels of ERK1 and ERK2. In addition, the expression of MAP kinase phosphatase (MKP)2, a ‘dual function’ ERK1/2 phosphatase, was increased in the prefrontal cortex and hippocampus. These studies suggest that p44/42 MAP kinases are less activated in the post‐mortem brain of depressed suicide subjects and this may be because of reduced expression of ERK1/2 and increased expression of MKP2. Given the role of MAP kinases in various physiological functions and gene expression, alterations in p44/42 MAP kinase activation and expression of ERK1/2 may contribute significantly to the pathophysiology of depressive disorders.