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

Abstract

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.

• Authors: Y Dwivedi, H S Rizavi, R C Roberts, R C Conley, C A Tamminga, G N Pandey
• Journal: Journal of neurochemistry (J Neurochem) Vol. 77 Issue 3 Pg. 916-28 (May 2001) ISSN: 0022-3042 [Print] England
• PMID: 11331420 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• RNA, Messenger
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinase Phosphatases
• DUSP4 protein, human
• Dual-Specificity Phosphatases
• Protein Tyrosine Phosphatases

Topics

• Adult
• Aged
• Brain (enzymology)
• Cell Membrane (enzymology)
• Cell Nucleus (enzymology)
• Cytosol (enzymology)
• Depression (enzymology)
• Dual-Specificity Phosphatases
• Enzyme Activation
• Female
• Gene Expression
• Hippocampus (enzymology)
• Humans
• Male
• Middle Aged
• Mitogen-Activated Protein Kinase 1 (analysis, genetics, metabolism)
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinase Phosphatases
• Mitogen-Activated Protein Kinases (analysis, genetics, metabolism)
• Phosphorylation
• Prefrontal Cortex (enzymology)
• Protein Tyrosine Phosphatases (analysis, metabolism)
• RNA, Messenger (analysis)
• Suicide