Increased expression of c-Jun transcription factor in cerebellar vermis of patients with schizophrenia.
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.
Todorova
Valentina K
VK
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, USA.
Elbein
Alan D
AD
Kyosseva
Svetlana V
SV
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000818:Animals; D002531:Cerebellum / Q000378:metabolism*; D016009:Chi-Square Distribution; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*; D018709:Statistics, Nonparametric
D016755:Proto-Oncogene Proteins c-jun