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.

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.