Altered levels of extracellular signal-regulated kinase signaling proteins in postmortem frontal cortex of individuals with mood disorders and schizophrenia.

Abstract

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
• Journal: Journal of affective disorders (J Affect Disord) Vol. 124 Issue 1-2 Pg. 164-9 (Jul 2010) ISSN: 1573-2517 [Electronic] Netherlands
• PMID: 19913919 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• CREB1 protein, human
• Cyclic AMP Response Element-Binding Protein
• Shelterin Complex
• TERF2IP protein, human
• Telomere-Binding Proteins
• MAP2K2 protein, human
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• RPS6KA1 protein, human
• Ribosomal Protein S6 Kinases, 90-kDa
• Extracellular Signal-Regulated MAP Kinases
• Mitogen-Activated Protein Kinase 3
• MAP Kinase Kinase 1
• MAP Kinase Kinase 2
• MAP2K1 protein, human
• Phosphopyruvate Hydratase

Topics

• 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)
• Shelterin Complex
• Telomere-Binding Proteins (analysis)