Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects.
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.
Dwivedi
Y
Y
Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 60612, USA. ydwivedi@psych.uic.edu
Rizavi
H S
HS
Roberts
R C
RC
Conley
R C
RC
Tamminga
C A
CA
Pandey
G N
GN
D000328:Adult; D000368:Aged; D001921:Brain / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D002467:Cell Nucleus / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D003863:Depression / Q000201:enzymology*; D054637:Dual-Specificity Phosphatases; D004789:Enzyme Activation; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000201:enzymology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D054639:Mitogen-Activated Protein Kinase Phosphatases; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D017397:Prefrontal Cortex / Q000201:enzymology; D017027:Protein Tyrosine Phosphatases / Q000032:analysis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D013405:Suicide
D012333:RNA, Messenger; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D054639:Mitogen-Activated Protein Kinase Phosphatases; C490583:DUSP4 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases