Reconstruction of neural network in schizophrenia ： Possible combined therapy of drugs and stem cells

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  • Ukai Wataru
    Department of Neuropsychiatry, Sapporo Medical University, School of Medicine
  • Ono Takafumi
    Department of Neuropsychiatry, Sapporo Medical University, School of Medicine
  • Hashimoto Eri
    Department of Neuropsychiatry, Sapporo Medical University, School of Medicine
  • Kaneta Hiroo
    Department of Neuropsychiatry, Sapporo Medical University, School of Medicine
  • Shirasaka Tomohiro
    Department of Neuropsychiatry, Sapporo Medical University, School of Medicine
  • Igarashi Takeshi
    Department of Neuropsychiatry, Sapporo Medical University, School of Medicine
  • Kigawa Yoshiyasu
    Department of Neuropsychiatry, Sapporo Medical University, School of Medicine
  • Watanabe Kimihiko
    Department of Neuropsychiatry, Sapporo Medical University, School of Medicine
  • Yoshinaga Toshihiro
    Department of Neuropsychiatry, Sapporo Medical University, School of Medicine
  • Ishii Takao
    Department of Neuropsychiatry, Sapporo Medical University, School of Medicine
  • Tateno Masaru
    Department of Neuropsychiatry, Sapporo Medical University, School of Medicine
  • Kobayashi Seiju
    Department of Neuropsychiatry, Sapporo Medical University, School of Medicine
  • Saito Toshikazu
    Department of Neuropsychiatry, Sapporo Medical University, School of Medicine

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Other Title
  • 統合失調症の脳神経回路修復─薬物・細胞コンバインド療法の可能性の検討
  • 統合失調症の脳神経回路修復―薬物・細胞コンバインド療法の可能性の検討
  • トウゴウ シッチョウショウ ノ ノウ シンケイ カイロ シュウフク ― ヤクブツ ・ サイボウ コンバインド リョウホウ ノ カノウセイ ノ ケントウ

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Abstract

We constructed schizophrenia model rat by injection of Poly (I : C) in the maternal period. Animals in the Poly (I : C) treatment group showed a significant memory/cognitive impairment and social dysfunction in each behavioral test and intravenous neural stem cell transplantation suppressed these behavioral abnormalities toward control levels. The transplanted marked neural stem cells were detected in the various brain regions including cingulated cortex, hippocampus and amygdale over 6 months after the intravenous injection. Specifically, we detected the transplanted neural stem cells in hippocampus and amygdale which were positive with GAD protein suggesting the successful differentiation of transplanted cells into GABAergic neurons in these areas. Moreover, it was demonstrated that combined treatment of antipsychotic olanzapine promoted the migration/survival of transplanted neural stem cells in the brain. These results suggest that drug with stem cell transplantation must develop to a possible therapeutic approach for fetal and childhood stress related psychiatric disease such as schizophrenia and fetal alcohol spectrum disorder.

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