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

Y. Dwivedi, H. S. Rizavi, R. C. Roberts, R. C. Conley, C. A. Tamminga, G. N. Pandey

Research output: Contribution to journalArticlepeer-review

253 Scopus citations

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 codex 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.

Original languageEnglish (US)
Pages (from-to)916-928
Number of pages13
JournalJournal of Neurochemistry
Volume77
Issue number3
DOIs
StatePublished - 2001

Keywords

  • Depression
  • ERK1/2
  • Human post-mortem brain
  • MKP2
  • Suicide
  • p42/44 MAP kinases

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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