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Reduced activation and expression of ERK1/2 MAP kinase in the post‐mortem brain of depressed suicide subjects
Author(s) -
Dwivedi Y.,
Rizavi H. S.,
Roberts R. C.,
Conley R. C.,
Tamminga C. A.,
Pandey G. N.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00300.x
Subject(s) - kinase , mitogen activated protein kinase , hippocampus , mapk/erk pathway , phosphatase , prefrontal cortex , medicine , endocrinology , neuroscience , biology , phosphorylation , microbiology and biotechnology , cognition
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.