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Keap1–Nrf2 signaling pathway confers resilience versus susceptibility to inescapable electric stress

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Abstract

The transcription factor Keap1–Nrf2 signaling plays a key role in the oxidative stress which is involved in psychiatric disorders. In the learned helplessness (LH) paradigm, protein levels of Keap1 and Nrf2 in the prefrontal cortex and dentate gyrus of hippocampus from LH (susceptible) rats were lower than control and non-LH (resilience) rats. Furthermore, protein expressions of Keap1 and Nrf2 in the parietal cortex from major depressive disorder, schizophrenia, and bipolar disorder were lower than controls. These results suggest that Keap1–Nrf2 signaling might contribute to stress resilience which plays a key role in the pathophysiology of psychiatric disorders.

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Acknowledgements

We thank to The Stanley Medical Research Institution (MD, USA) for providing the postmortem tissue samples. This study was supported by the Strategic Research Program for Brain Sciences from Japan Agency for Medical Research and Development, AMED (to KH), a Grant-in-Aid for Scientific Research (B) from Japan Society for the Promotion of Science (JSPS) (to KH, 17H04243), and a Grant-in-Aid for Young Scientists (B) from JSPS (to JCZ, 15K19711). Dr. Wei Yao was supported by Ishidsu Shun Memorial Scholarship (Tokyo, Japan). Dr. Chao Dong was supported by Uehara Memorial Foundation (Tokyo, Japan). Dr. Mei Han was supported by Postdoctoral Fellowship for Overseas Researchers of JSPS (Tokyo, Japan).

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Authors and Affiliations

  1. Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, 260-8670, Japan

    Ji-chun Zhang, Wei Yao, Chao Dong, Mei Han, Yukihiko Shirayama & Kenji Hashimoto

  2. Department of Psychiatry, Teikyo University Chiba Medical Center, Ichihara, Japan

    Yukihiko Shirayama

Authors
  1. Ji-chun Zhang
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  2. Wei Yao
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  3. Chao Dong
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  4. Mei Han
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  5. Yukihiko Shirayama
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  6. Kenji Hashimoto
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Contributions

JCZ and KH conceived and designed this study. JCZ, WY, CD, MH, and YS performed the experiments. JCZ and KH wrote the manuscript. All the authors read and approved this manuscript.

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Correspondence to Kenji Hashimoto.

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The authors declare no conflict of interest.

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Zhang, Jc., Yao, W., Dong, C. et al. Keap1–Nrf2 signaling pathway confers resilience versus susceptibility to inescapable electric stress. Eur Arch Psychiatry Clin Neurosci 268, 865–870 (2018). https://doi.org/10.1007/s00406-017-0848-0

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  • DOI: https://doi.org/10.1007/s00406-017-0848-0

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