Elevation of EGR1/zif268, a Neural Activity Marker, in the Auditory Cortex of Patients with Schizophrenia and its Animal Model

Yuriko Iwakura, Ryoka Kawahara-Miki, Satoshi Kida, Hidekazu Sotoyama, Ramil Gabdulkhaev, Hitoshi Takahashi, Yasuto Kunii, Mizuki Hino, Atsuko Nagaoka, Ryuta Izumi, Risa Shishido, Toshiyuki Someya, Hirooki Yabe, Akiyoshi Kakita, Hiroyuki Nawa

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


The family of epidermal growth factor (EGF) including neuregulin-1 are implicated in the neuropathology of schizophrenia. We established a rat model of schizophrenia by exposing perinatal rats to EGF and reported that the auditory pathophysiological traits of this model such as prepulse inhibition, auditory steady-state response, and mismatch negativity are relevant to those of schizophrenia. We assessed the activation status of the auditory cortex in this model, as well as that in patients with schizophrenia, by monitoring the three neural activity-induced proteins: EGR1 (zif268), c-fos, and Arc. Among the activity markers, protein levels of EGR1 were significantly higher at the adult stage in EGF model rats than those in control rats. The group difference was observed despite an EGF model rat and a control rat being housed together, ruling out the contribution of rat vocalization effects. These changes in EGR1 levels were seen to be specific to the auditory cortex of this model. The increase in EGR1 levels were detectable at the juvenile stage and continued until old ages but displayed a peak immediately after puberty, whereas c-fos and Arc levels were nearly indistinguishable between groups at all ages with an exception of Arc decrease at the juvenile stage. A similar increase in EGR1 levels was observed in the postmortem superior temporal cortex of patients with schizophrenia. The commonality of the EGR1 increase indicates that the EGR1 elevation in the auditory cortex might be one of the molecular signatures of this animal model and schizophrenia associating with hallucination.

Original languageEnglish
Pages (from-to)2715-2727
Number of pages13
JournalNeurochemical Research
Issue number9
Publication statusPublished - 2022 Sept


  • Auditory cortex
  • Auditory hallucination
  • Early growth response 1
  • Epidermal growth factor
  • Immediate early gene
  • Schizophrenia

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Elevation of EGR1/zif268, a Neural Activity Marker, in the Auditory Cortex of Patients with Schizophrenia and its Animal Model'. Together they form a unique fingerprint.

Cite this