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Antidepressants Modulate Microglia Beyond the Neurotransmitters Doctrine of Mood Disorders

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Melatonin, Neuroprotective Agents and Antidepressant Therapy

Abstract

Mood disorders have long and dominantly been regarded to be induced by disturbances of neuronal networks including synapses and neurotransmitters. Thus, the effects of psychotropic drugs including antidepressants have long been understood to modulate synaptic regulation via receptors and transporters of neurotransmitters such as serotonin. Recently, microglia, immune cells in the brain, have been indicated to have positive links to psychiatric disorders. Human imaging studies have shown microglial activation in the brain of patients with neuropsychiatric disorders such as depression and schizophrenia especially suicide victims. Animal models of psychiatric disorders including depression models have revealed the underlying microglial pathologies. In addition, various psychotropic drugs have been suggested to have direct effects on microglia. We herein introduce up-to-date knowledge of the effects of antidepressants on microglial modulation. In addition, we summarize recent findings of the interaction between microglia and neurotransmitters such as serotonin and melatonin. Finally, we propose the possibility that modulating microglia may be a key target in the treatment of various psychiatric disorders. Further translational investigations should be conducted to clarify this perspective, using rodent in vivo models, and novel translational research techniques such as directly induced microglia-like (iMG) cells from human peripheral blood.

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Acknowledgments

This work was supported by Grant-in-Aid for Scientific Research on (1) the Japan Society for the Promotion of Science, KAKENHI (to TAK (24650227&26713039) and SK (25293252)); (2) Innovative Areas “Glia Assembly” of The Ministry of Education, Culture, Sports, Science, and Technology, Japan (25117011 to SK); (3) the Japan Agency for Medical Research and Development (AMED), the Japanese Ministry of Health, Labour, and Welfare (H27 – Seishin-Syogai Taisaku-Jigyo to SK); (4) the Young Principal Investigators’ Research Grant of Innovation Center for Medical Redox Navigation, Kyushu University (to TAK); (5) the Takeda Science Foundation, Medical Research (to TAK); and (6) the SENSHIN Medical Research Foundation (to TAK, MO & SK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan

    Masahiro Ohgidani PhD, Takahiro A. Kato MD, PhD, Hideki Horikawa MD, PhD & Shigenobu Kanba MD, PhD

  2. Brain Research Unit, Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka, 812-8582, Japan

    Takahiro A. Kato MD, PhD

  3. Department of Psychiatry, Faculty of Medicine, Saga University, Saga, Japan

    Yoshito Mizoguchi MD, PhD & Akira Monji MD, PhD

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  1. Masahiro Ohgidani PhD
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  2. Takahiro A. Kato MD, PhD
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  3. Yoshito Mizoguchi MD, PhD
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  4. Hideki Horikawa MD, PhD
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  5. Akira Monji MD, PhD
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  6. Shigenobu Kanba MD, PhD
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Corresponding author

Correspondence to Takahiro A. Kato MD, PhD .

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Editors and Affiliations

  1. Vice-Rectorate for Research and Sci, Camilo José Cela University Vice-Rectorate for Research and Sci, Madrid, Spain

    Francisco López-Muñoz

  2. International Medical Sciences Research Study Center, Sri Sathya Sai Medical Educational & Research Foundation, Coimbatore, India

    Venkataramanujam Srinivasan

  3. Department of Neurosciences and Ima, University of Chieti Department of Neurosciences and Ima, Italy, Italy

    Domenico de Berardis

  4. Department of Biomedical Sciences (Pharmacology Area), University of Alcalá, Madrid, Spain

    Cecilio Álamo

  5. Department of Neuropsychiatry, Kyushu University, Fukuoka, Japan

    Takahiro A. Kato

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All authors declare that they have no financial conflict of interest.

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© 2016 Springer India

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Ohgidani, M., Kato, T.A., Mizoguchi, Y., Horikawa, H., Monji, A., Kanba, S. (2016). Antidepressants Modulate Microglia Beyond the Neurotransmitters Doctrine of Mood Disorders. In: López-Muñoz, F., Srinivasan, V., de Berardis, D., Álamo, C., Kato, T. (eds) Melatonin, Neuroprotective Agents and Antidepressant Therapy. Springer, New Delhi. https://doi.org/10.1007/978-81-322-2803-5_36

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  • DOI: https://doi.org/10.1007/978-81-322-2803-5_36

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  • Online ISBN: 978-81-322-2803-5

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