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Increased expression of c-Jun transcription factor in cerebellar vermis of patients with schizophrenia
Valentina K Todorova1, Alan D Elbein, Svetlana V Kyosseva
1Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, USA.
Abstract:
In the cerebellar vermis of schizophrenic patients, our previous studies have revealed alterations in the mitogen-activated protein (MAP) kinase signaling cascade and downstream transcription factors within the c-fos promoter. Since the proteins of the Fos and Jun families of immediate-early genes dimerize to form activating protein (AP)-1, the present study was conducted to examine the expression of Jun transcription factors in schizophrenic and control subjects. Using Western blot analysis, we determined the protein levels of c-Jun, Jun B, and Jun D as well as the levels of c-jun mRNA by relative RT-PCR in post-mortem samples from cerebellar vermis. The expression of c-Jun protein and c-jun mRNA was significantly increased in the cerebellar vermis of patients with schizophrenia, whereas no significant differences were found in the expression of Jun B or Jun D proteins. Studies in rats indicated that the abnormal expression of c-Jun transcription factor observed in schizophrenic patients was not related to post-mortem intervals or chronic treatment with antipsychotic medications. This study provides new insights into cerebellar abnormalities of schizophrenia at the level of expression of c-Jun that target key genes associated with the MAP kinase cascade.
Insights
Schizophrenia is linked to increased c-Jun protein and mRNA in the cerebellum, a key part of the mitogen-activated protein (MAP) kinase pathway. This finding offers new insights into cerebellar abnormalities in schizophrenia.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Previous research identified alterations in the MAP kinase signaling cascade and c-fos promoter transcription factors in the cerebellar vermis of schizophrenia patients.
- The Fos and Jun protein families form activating protein (AP)-1, crucial for gene regulation.
Purpose of the Study:
- To investigate the expression of Jun transcription factors (c-Jun, Jun B, Jun D) in the cerebellar vermis of individuals with schizophrenia compared to controls.
- To determine if observed abnormalities in Jun transcription factor expression are related to post-mortem intervals or antipsychotic medication use.
Main Methods:
- Western blot analysis was used to quantify protein levels of c-Jun, Jun B, and Jun D.
- Relative reverse transcription polymerase chain reaction (RT-PCR) was employed to measure c-jun mRNA levels.
- Post-mortem cerebellar vermis samples from schizophrenic patients and control subjects were analyzed.
Main Results:
- Significantly elevated levels of c-Jun protein and c-jun mRNA were observed in the cerebellar vermis of schizophrenia patients.
- No significant differences in Jun B or Jun D protein expression were found between patient and control groups.
- Animal studies suggested that the abnormal c-Jun expression was not influenced by post-mortem intervals or chronic antipsychotic treatment.
Conclusions:
- The study reveals a specific upregulation of c-Jun in the cerebellar vermis of schizophrenia patients, highlighting its role in cerebellar abnormalities.
- These findings contribute to understanding the molecular mechanisms underlying schizophrenia, particularly concerning the MAP kinase pathway and immediate-early gene regulation.
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