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Midkine in Psychiatric and Neurodegenerative Diseases

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Midkine: From Embryogenesis to Pathogenesis and Therapy

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Abstract

Midkine (MK) is strongly expressed during the midgestation period of embryogenesis, while its expression is nearly undetectable in the normal adult brain. However, recent evidences suggest that MK may play various roles in the pathological phenomena of the adult brain. MK binds strongly to Abeta peptides and neutralizes its cytotoxic activity. The findings about elevated MK levels in brain and serum of patients with Alzheimer disease (AD) suggest that MK may be induced to counteract Abeta-related pathophysiology in AD. On the other hand, MK was found to promote the survival of mouse mesencephalic (mainly dopaminergic) neurons in culture. Midkine-deficient (Mdk(−/−)) mice transiently exhibited a delay in postnatal hippocampal development with a working memory deficit and increased anxiety only at the age of 4 weeks. Adult Mdk(−/−) mice exhibited a hypodopaminergic state in the striatum, the prepulse inhibition deficits, and social interaction impairments. These findings suggested that midkine may contribute to the pathophysiology of dopamine-related disorders including schizophrenia and Parkinson’s disease.

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Acknowledgments

I thank Dr. Shintaro Ohgake, Prof. Masaomi Iyo (Department of Psychiatry, Chiba University Graduate School of Medicine), Prof. Kenji Hashimoto (Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health), Prof. Hisako Muramatsu, and Prof. Takashi Muramatsu (Department of Health Science, Faculty of Psychological and Physical Sciences, Aichi Gakuin University), whose work has been integral to the development of this review paper.

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Authors and Affiliations

  1. Department of Cognitive Behavioral Physiology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan

    Eiji Shimizu & Daisuke Matsuzawa

Authors
  1. Eiji Shimizu
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  2. Daisuke Matsuzawa
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Corresponding author

Correspondence to Eiji Shimizu .

Editor information

Editors and Affiliations

  1. Faculty of Medicine, Faculty of Biochemistry, Yeni Yüzyıl University, Yilanli Ayazma 26, Istanbul, 34000, Istanbul, Turkey

    Mine Ergüven

  2. , Department of Health Science, Aichi Gakuin University, 12 Araike, Iwasakicho, Nisshin, Aichi, Japan

    Takashi Muramatsu

  3. , Department of Histology and Embryology, Istanbul University Faculty of Medicine, Millet, Istanbul, Turkey

    Ayhan Bilir

Additional information

Funding: This research was supported by the Grant-in-Aid for Scientific Research of the Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT Grant 18500289&21500344).

Conflict of interest:  We have no conflicts of interest to disclose.

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Shimizu, E., Matsuzawa, D. (2012). Midkine in Psychiatric and Neurodegenerative Diseases. In: Ergüven, M., Muramatsu, T., Bilir, A. (eds) Midkine: From Embryogenesis to Pathogenesis and Therapy. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4234-5_14

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