Document Detail


Altered levels of extracellular signal-regulated kinase signaling proteins in postmortem frontal cortex of individuals with mood disorders and schizophrenia.
MedLine Citation:
PMID:  19913919     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The extracellular-regulated protein kinase (ERK) pathway has been implicated in processes such as neuronal plasticity and resilience in psychiatric disorders including major depressive disorder (MDD), bipolar disorder (BPD), and schizophrenia. The extent of the possible involvement of this pathway in psychiatric disorders remains unknown, as does its potential utility as a pharmacological target for the future development of novel therapeutics.
METHODS: Western blot analyses were used to measure levels of different proteins-Rap1, B-Raf, MEK1, MEK2, ERK1/2, RSK1, CREB, NSE, and beta-actin-in the postmortem frontal cortex of individuals with schizophrenia, MDD, and BPD, as well as healthy non-psychiatric controls.
RESULTS: Levels of most studied protein members of the ERK cascade were lower in individuals with psychiatric disorders than controls; differences between psychiatric groups were not statistically significant. In general, protein levels were lower in individuals with schizophrenia than in those with BPD or MDD, but protein levels varied across groups.
LIMITATIONS: The small number of individuals in each diagnostic group may limit our interpretation of the results. Factors such as postmortem interval, medication status at time of death, and mood state at time of death may also have influenced the findings.
DISCUSSION: The results are consistent with the hypothesis that the ERK pathway is implicated in reduced neuronal plasticity associated with the course of these psychiatric illnesses. The results warrant an expanded investigation into the activity of other members of this pathway as well as other brain areas of interest.
Authors:
Peixiong Yuan; Rulun Zhou; Yun Wang; Xiaoxia Li; Jianling Li; Guang Chen; Xavier Guitart; Husseini K Manji
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2009-11-13
Journal Detail:
Title:  Journal of affective disorders     Volume:  124     ISSN:  1573-2517     ISO Abbreviation:  J Affect Disord     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-05-24     Completed Date:  2010-08-23     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  7906073     Medline TA:  J Affect Disord     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  164-9     Citation Subset:  IM    
Affiliation:
Biomarker Laboratory, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Actins / analysis
Adult
Bipolar Disorder / pathology*
Blotting, Western
Cyclic AMP Response Element-Binding Protein / analysis
Depressive Disorder, Major / pathology*
Extracellular Signal-Regulated MAP Kinases / analysis*
Female
Frontal Lobe / pathology*
Humans
MAP Kinase Kinase 1 / analysis
MAP Kinase Kinase 2 / analysis
Male
Middle Aged
Mitogen-Activated Protein Kinase 3 / analysis
Neuronal Plasticity / physiology
Phosphopyruvate Hydratase / analysis
Proto-Oncogene Proteins B-raf / analysis
Reference Values
Ribosomal Protein S6 Kinases, 90-kDa / analysis
Schizophrenia / pathology*
Telomere-Binding Proteins / analysis
Grant Support
ID/Acronym/Agency:
ZIA MH002921-01/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Actins; 0/CREB1 protein, human; 0/Cyclic AMP Response Element-Binding Protein; 0/TERF2IP protein, human; 0/Telomere-Binding Proteins; EC 2.7.1.-/MAP2K1 protein, human; EC 2.7.1.-/MAP2K2 protein, human; EC 2.7.11.1/BRAF protein, human; EC 2.7.11.1/Proto-Oncogene Proteins B-raf; EC 2.7.11.1/RPS6KA1 protein, human; EC 2.7.11.1/Ribosomal Protein S6 Kinases, 90-kDa; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 2.7.12.2/MAP Kinase Kinase 1; EC 2.7.12.2/MAP Kinase Kinase 2; EC 4.2.1.11/Phosphopyruvate Hydratase
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