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Neurotoxin Modeling of Brain Disorders—Life-long Outcomes in Behavioral Teratology pp 429–446Cite as

Pathological Implications of Oxidative Stress in Patients and Animal Models with Schizophrenia: The Role of Epidermal Growth Factor Receptor Signaling

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Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 29))

Abstract

Proinflammatory cytokines perturb brain development and neurotransmission and are implicated in various psychiatric diseases, such as schizophrenia and depression. These cytokines often induce the production of reactive oxygen species (ROS) and regulate not only cell survival and proliferation but also inflammatory process and neurotransmission. Under physiological conditions, ROS are moderately produced in mitochondria but are rapidly scavenged by reducing agents in cells. However, brain injury, ischemia, infection, or seizure-like neural activities induce inflammatory cytokines and trigger the production of excessive amounts of ROS, leading to abnormal brain functions and psychiatric symptoms. Protein phosphatases, which are involved in the basal silencing of cytokine receptor activation, are the major targets of ROS. Consistent with this, several ROS scavengers, such as polyphenols and unsaturated fatty acids, attenuate both cytokine signaling and psychiatric abnormalities. In this review, we list the inducers, producers, targets, and scavengers of ROS in the brain and discuss the interaction between ROS and cytokine signaling implicated in schizophrenia and its animal models. In particular, we present an animal model of schizophrenia established by perinatal exposure to epidermal growth factor and illustrate the pathological role of ROS and antipsychotic actions of ROS scavengers, such as emodin and edaravone.

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Acknowledgments

We are grateful to Tomoyuki Sugano and Akira Yarimizu for their technical assistances. The authors’ original work was partly supported by Grants-in-Aid for Scientific Research on Innovative Areas and for Challenging Exploratory Research (No. 24116010, No. 21659273) and a grant for Promotion of Niigata University Research Projects. Human recombinant EGF was kindly provided by Higeta Shoyu Co. Ltd. Except this gift, all the authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Faculty of Human Life Studies, University of Niigata Prefecture, 471 Ebigase, Higashi-ku, Niigata, 950-8680, Japan

    Tadasato Nagano

  2. Aichi Human Service Center, Institute for Developmental Research, Kasugai, Aichi, 480-0392, Japan

    Makoto Mizuno

  3. Department of Molecular Biology, Brain Research Institute, Niigata University, Asahimachi-Dori 1-757, Niigata, 951-8585, Japan

    Keisuke Morita & Hiroyuki Nawa

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  1. Tadasato Nagano
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  2. Makoto Mizuno
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  4. Hiroyuki Nawa
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Correspondence to Hiroyuki Nawa .

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Editors and Affiliations

  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN, USA

    Richard M. Kostrzewa

  2. Department of Psychology, University of Gothenburg, Gothenburg, Sweden

    Trevor Archer

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Nagano, T., Mizuno, M., Morita, K., Nawa, H. (2015). Pathological Implications of Oxidative Stress in Patients and Animal Models with Schizophrenia: The Role of Epidermal Growth Factor Receptor Signaling. In: Kostrzewa, R.M., Archer, T. (eds) Neurotoxin Modeling of Brain Disorders—Life-long Outcomes in Behavioral Teratology. Current Topics in Behavioral Neurosciences, vol 29. Springer, Cham. https://doi.org/10.1007/7854_2015_399

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