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.
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Acknowledgements
This study was supported by the National Institute of Mental Health Grant MH 60739 (SVK) and the Marie Wilson Howells Endowment of the Department of Psychiatry at the University of Arkansas for Medical Sciences. We gratefully acknowledge WS Griffin, PhD and RE Mrak, MD, PhD from University of Arkansas for Medical Sciences for providing us with autopsied human brains and for their helpful comments and suggestions.
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Todorova, V., Elbein, A. & Kyosseva, S. Increased Expression of c-Jun Transcription Factor in Cerebellar Vermis of Patients with Schizophrenia. Neuropsychopharmacol 28, 1506–1514 (2003). https://doi.org/10.1038/sj.npp.1300211
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DOI: https://doi.org/10.1038/sj.npp.1300211
