The new therapeutic approach for schizophrenia treatment-study of the combined therapy using drug and cells-

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591374
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Sapporo Medical University
• Principal Investigator: UKAI Wataru Sapporo Medical University, 医学部, 講師 (40381256)
• Co-Investigator(Kenkyū-buntansha): HASHIMOTO Eri 札幌医科大学, 医学部, 准教授 (30301401) ; TATENO Masaru 札幌医科大学, 医学部, 講師 (60464492) ; YOSHINAGA Toshihiro 札幌医科大学, 医学部, 助教 (70404704) ; ONO Takafumi 札幌医科大学, 医学部, 研究員 (50438024)
• Project Period (FY): 2008 – 2010
• Keywords: 精神薬理学

Research 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.

Research Products

• [Journal Article] Neuroserpin is expressed in early stage of neurogenesis in adult rat hippocampus. (2010)
  • Author(s): Yamada M, Takahashi K, Ukai W, Hashimoto E, Saito T, Yamada. M.
  • Journal Title: Neuroreport 21 Pages: 138-142
  • Peer Reviewed
• [Journal Article] The role of neural stem cells for in vitro models of schizophrenia : Neuroprotection via Akt/ERK signal regulation. (2010)
  • Author(s): 小野貴文, 橋本恵理, 鵜飼渉, 石井貴男, 齋藤利和
  • Journal Title: Schizophr Res 122 Pages: 239-247
  • Peer Reviewed
• [Journal Article] Effect of antidepressants on brain-derived neurotrophic factor (BDNF) release from platelets in the rats. (2010)
  • Author(s): 渡邊公彦, 橋本恵理, 鵜飼渉, 石井貴男, 吉永敏弘, 小野貴文, 館農勝, 渡邉一平, 白坂知彦, 齋藤諭, 齋藤利和
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry 34 Pages: 1450-1454
  • Peer Reviewed
• [Journal Article] Pervasive Developmental Disorders and Autism Spectrum Disorders : Are These Disorders One and the Same (2010)
  • Author(s): Tateno M, Kikuchi S, Uehara K, Fukita K, Uchida N, Sasaki R, Saito T
  • Journal Title: Psychiatry Investigation 8 Pages: 67-70
  • Peer Reviewed
• [Journal Article] 精神障害が併存するアルコール依存症の病態と治療 アルコール依存症と気分障害 (2010)
  • Author(s): 橋本恵理, 齋藤利和
  • Journal Title: 精神神経学雑誌 112 Pages: 780-786
• [Journal Article] ストレスによる脳神経回路網変異-障害と修復の分子メカニズム- (2010)
  • Author(s): 鵜飼渉, 橋本恵理, 吉永敏弘, 白坂知彦, 渡邊公彦, 渡邉一平, 金田博雄, 館農勝, 石井貴男, 齋藤利和
  • Journal Title: ストレス科学 25 Pages: 167-177
• [Journal Article] Low serum BDNF and food intake regulation : a possible new explanation of the pathophysiology of eating disorders. (2009)
  • Author(s): 齋藤諭, 渡邊公彦, 橋本恵理, 齋藤利和
  • Journal Title: Prog Neuropsychopharmacol Biol Psychiatry 33 Pages: 312-316
  • Peer Reviewed
• [Journal Article] Effects of typical (haloperidol) and atypical (risperidone) antipsychotic agents on protein expression in rat neural stem cells. (2009)
  • Author(s): Kashem MA, Ummehany R, Ukai W, Hashimoto E, Saito T, McGregor IS, Matsumoto I.
  • Journal Title: Neurochem Int 55 Pages: 558-565
  • Peer Reviewed
• [Journal Article] 気分障害における神経回路網の修復再生と認知機能 (2009)
  • Author(s): 鵜飼渉, 橋本恵理, 石井貴男, 吉永敏弘, 渡邊公彦, 小野貴文, 館農勝, 渡邉一平, 白坂智彦, 齋藤利和
  • Journal Title: 臨床精神医学 38 Pages: 421-428
• [Journal Article] 非定型抗精神病薬の神経新生作用 (2009)
  • Author(s): 橋本恵理, 鵜飼渉, 小野貴文, 齋藤利和
  • Journal Title: 脳21 12 Pages: 195-199
• [Journal Article] アルコールによる脳障害に対する再生医療的アプローチの可能性 (2009)
  • Author(s): 橋本恵理, 吉永敏弘, 石井貴男, 齋藤諭, 鵜飼渉, 齋藤利和
  • Journal Title: 日本アルコール・薬物医学会雑誌 44 Pages: 674-679
• [Journal Article] The common aspects of pathophysiology of alcoholism and depression. (2009)
  • Author(s): 鵜飼渉, 石井貴男, 橋本恵理, 館農勝, 吉永敏弘, 小野貴文, 渡邊公彦, 渡邉一平, 白坂知彦, 齋藤利和
  • Journal Title: 日本アルコール・薬物医学会雑誌 44 Pages: 704-711
• [Journal Article] Biological studies on alcohol-induced neuronal damage. (2008)
  • Author(s): 館農勝, 齋藤利和
  • Journal Title: Psychiatry Investigation 5 Pages: 21-27
  • Peer Reviewed
• [Journal Article] Lithium-induced suppression of transcription repressor NRSF/REST : Effects on the dysfunction of neuronal differentiation by ethanol. (2008)
  • Author(s): Ishii T, Hashimoto E, Ukai W, Tateno M, Yoshinaga T, Saito S, Sohma H, Saito T
  • Journal Title: Eur J Pharmacol 593 Pages: 36-43
  • Peer Reviewed
• [Journal Article] アルコールによる脳神経回路網の異常 神経幹細胞を用いた修復の試み (2008)
  • Author(s): 鵜飼渉, 橋本恵理, 吉永敏弘, 石井貴男, 館農勝, 小野貴文, 渡邊公彦, 齋藤諭, 齋藤利和
  • Journal Title: 日本神経精神薬理学雑誌 28 Pages: 69-73
• [Journal Article] 神経新生と病態 薬物と神経新生 アルコール (2008)
  • Author(s): 館農勝, 齋藤利和
  • Journal Title: Clinical Neuroscience 26 Pages: 899-901
• [Journal Article] 薬物と神経新生 向精神薬 (2008)
  • Author(s): 橋本恵理, 小野貴文, 渡邉公彦
  • Journal Title: Clinical Neuroscience 26 Pages: 887-889
• [Journal Article] 新規抗精神病薬の開発動向 (2008)
  • Author(s): 鵜飼渉, 橋本恵理, 齋藤利和
  • Journal Title: 脳と精神の医学 19 Pages: 173-179
• [Journal Article] アルコールによる脳障害とエピジェネティクス制御機構 (2008)
  • Author(s): 石井貴男, 橋本恵理, 鵜飼渉, 館農勝, 吉永敏弘, 小野貴文, 渡邊公彦, 齋藤諭, 齋藤利和
  • Journal Title: 日本アルコール・薬物医学会雑誌 43 Pages: 705-713
• [Journal Article] アルコールによる脳神経回路障害のメカニズムとその修復法の探索 神経細胞・神経幹細胞を用いたin vitro、in vivo解析 (2008)
  • Author(s): 鵜飼渉, 石井貴男, 吉永敏弘, 館農勝, 橋本恵理, 小野貴文, 渡邊公彦, 渡邉一平, 白坂智彦, 齋藤利和
  • Journal Title: 日本アルコール・薬物医学会雑誌 43 Pages: 763-769
• [Presentation] 神経幹細胞移植によるFASDモデルラット「社会脳」再生の試み (2011)
  • Author(s): 白坂知彦, 鵜飼渉, 吉永敏弘, 木川昌康, 渡邊公彦, 渡邉一平, 金田博雄, 館農勝, 橋本恵理, 齋藤利和
  • Organizer: 第10回日本再生医療学会総会
  • Place of Presentation: 東京
  • Year and Date: 20110301-20110302
• [Presentation] The Change of Brain-Derived Neurotrophic Factor and TrkB Receptor on Platelet in Depression. (2010)
  • Author(s): Saito T, Hashimoto E, Ukai W, Watanabe K, Watanabe I, Shirasaka T, Kaneta H, Kigawa M, Yoshinaga T, Tateno M, Park T, Ishii T
  • Organizer: 49th ACNP
  • Place of Presentation: Florida
  • Year and Date: 20101205-20101209
• [Presentation] The possible implicasion of TLX on the regulation of impulsive behavior : focusing on the neural stem cell dysfunctions by TLX change. (2010)
  • Author(s): Ukai W, Watanabe I, Hashimoto E, Watanabe K, Shirasaka T, Kaneta H, Kigawa M, Ono T, Ishii T, Yoshinaga T, Tateno M, Kobayashi S, Saito T
  • Organizer: 40th Neuroscience
  • Place of Presentation: San Diego
  • Year and Date: 20101113-20101117
• [Presentation] 核内レセプタ-TLXの神経幹細胞における働きと抑肝散の与える影響 (2010)
  • Author(s): 渡邉一平, 鵜飼渉, 橋本恵理, 渡邊公彦, 白坂知彦, 小野貴文, 館農勝, 齋藤利和
  • Organizer: 第32回日本生物学的精神医学会
  • Place of Presentation: 小倉
  • Year and Date: 20101007-20101009
• [Presentation] (Symposium) Effects of psychotropics on ER stress and its potential implication for the clinical effect. (2010)
  • Author(s): 鵜飼渉, 橋本恵理, 小野貴文, 吉永敏弘, 石井貴男, 渡邊公彦, 渡邉一平, 白坂知彦, 館農勝, 齋藤利和
  • Organizer: 17th CINP
  • Place of Presentation: Hong Kong
  • Year and Date: 20100606-20100610
• [Presentation] Stem cell therapy. functional recovery in a neurodevelopmental model of schizophrenia. (2010)
  • Author(s): 橋本恵理, 小野貴文, 鵜飼渉, 吉永敏弘, 石井貴男, 渡邊公彦, 渡邉一平, 白坂知彦, 館農勝, 齋藤利和
  • Organizer: 17th CINP
  • Place of Presentation: Hong Kong
  • Year and Date: 20100606-20100610
• [Presentation] Roles of nuclear receptor TLX in neural stem cell functions. (2010)
  • Author(s): 渡邉一平, 鵜飼渉, 小野貴文, 渡邊公彦, 白坂知彦, 石井貴男, 橋本恵理, 館農勝, 齋藤利和
  • Organizer: 17th CINP
  • Place of Presentation: Hong Kong
  • Year and Date: 20100606-20100610
• [Presentation] The change of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) receptor on platelet in depression. (2010)
  • Author(s): 渡邊公彦, 橋本恵理, 鵜飼渉, 石井貴男, 吉永敏弘, 館農勝, 渡邉一平, 白坂知彦, 金田博雄, 木川昌康, 齋藤利和
  • Organizer: 17th CINP
  • Place of Presentation: Hong Kong
  • Year and Date: 20100606-20100610
• [Presentation] 末梢BDNFの体内動態を解明する (2010)
  • Author(s): 渡邊公彦, 橋本恵理, 鵜飼渉, 吉永敏弘, 館農勝, 渡邉一平, 白坂知彦, 金田博雄, 木川昌康, 五十嵐健史, 齋藤利和
  • Organizer: 第29回躁うつ病の薬理・生化学的研究懇話会
  • Place of Presentation: 箱根
  • Year and Date: 2010-06-18
• [Presentation] (シンポジウム) ストレスによる脳神経回路網変異-障害と修復の分子メカニズム- (2009)
  • Author(s): 鵜飼渉, 橋本恵理, 吉永敏弘, 白坂知彦, 石井貴男, 館農勝, 小野貴文, 渡邊公彦, 渡邉一平, 齋藤利和
  • Organizer: 第25回日本ストレス学会学術総会,第27回日本青年期精神療法学会総会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 20091204-20091205
• [Presentation] How do ethanol and depression impair neural stem cell? Dysregulation of CREB, NRSF/REST and TLX. (2009)
  • Author(s): 石井貴男, 鵜飼渉, 吉永敏弘, 館農勝, 小野貴文, 渡邊公彦, 渡邉一平, 白坂知彦,橋本恵理, 齋藤利和
  • Organizer: 39th SfN
  • Place of Presentation: Chicago
  • Year and Date: 20091017-20091021
• [Presentation] Stem cell therapy as a new treatment strategy for schizophrenia. (2009)
  • Author(s): 鵜飼渉, 小野貴文, 橋本恵理, 吉永敏弘, 石井貴男, 渡邊公彦, 渡邉一平, 白坂知彦, 館農勝, 齋藤利和
  • Organizer: 39th SfN
  • Place of Presentation: Chicago
  • Year and Date: 20091017-20091021
• [Presentation] (Workshop) Endoplasmic reticulum stress and neurogenetic dysfunction in psychiatric disorder. (2009)
  • Author(s): 鵜飼渉, 橋本恵理, 館農勝, 小野貴文, 渡邊公彦, 渡邉一平, 白坂知彦, 吉永敏弘, 齋藤利和
  • Organizer: 4th CSSI
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 20091006-20091009
• [Presentation] (シンポジウム)末梢サイトカイン変化と精神疾患の病態について (2009)
  • Author(s): 鵜飼渉, 小野貴文, 渡邊公彦, 橋本恵理, 吉永敏弘, 石井貴男, 館農勝, 渡邉一平, 白坂知彦, 齋藤利和
  • Organizer: 第52回日本神経科学大会
  • Place of Presentation: 群馬
  • Year and Date: 20090621-20090624
• [Presentation] 神経細胞移植は統合失調症の慢性期症状を抑制する (2009)
  • Author(s): 小野貴文, 鵜飼渉, 白坂知彦, 吉永敏弘, 橋本恵理, 石井貴男, 館農勝, 渡邊公彦, 渡邉一平, 齋藤利和
  • Organizer: 第52回日本神経科学大会
  • Place of Presentation: 群馬
  • Year and Date: 20090621-20090624
• [Presentation] 神経新生の変化における攻撃性・衝動性のメカニズム (2009)
  • Author(s): 渡邉一平, 鵜飼渉, 小野貴文, 渡邊公彦, 白坂知彦, 橋本恵理, 石井貴男, 館農勝, 齋藤利和
  • Organizer: 第52回日本神経科学大会
  • Place of Presentation: 群馬
  • Year and Date: 20090621-20090624
• [Presentation] ヒト脳神経系細胞におけるDNAメチル化解析-全ゲノムメチル化量の定量とメチル化領域の個人間差異の検討- (2009)
  • Author(s): 岩本和也, 文東美紀, 上田順子, 中野陽子, 鵜飼渉, 橋本恵理, 齋藤利和, 加藤忠史
  • Organizer: 第31回日本生物学的精神医学会
  • Place of Presentation: 京都
  • Year and Date: 20090423-20090425
• [Presentation] (Symposium) The stem cell therapy as a possible new treatment for schizophrenia. (2009)
  • Author(s): 橋本恵理, 鵜飼渉, 小野貴文, 吉永敏弘, 石井貴男, 館農勝, 渡邊公彦, 齋藤利和
  • Organizer: 第4回日本統合失調症学会
  • Place of Presentation: 大阪
  • Year and Date: 20090130-20090131
• [Presentation] 攻撃性・衝動性のメカニズムにおける神経新生異常の重要性に関する研究 (2009)
  • Author(s): 渡邉一平, 鵜飼渉, 小野貴文, 渡邊公彦, 白坂知彦, 橋本恵理, 石井貴男, 館農勝, 齋藤利和
  • Organizer: 第18回神経行動薬理若手研究者の集い
  • Place of Presentation: 横浜
  • Year and Date: 2009-03-19
• [Presentation] DNA methylation analysis in the human brain : separation of neuronal and non-neuronal nuclei by cell sorting. (2008)
  • Author(s): Bundo M, Iwamoto K, Nakano Y, Ueda J, Ukai W, Hashimoto E, Saito T, Kato T
  • Organizer: 16th WCPG
  • Place of Presentation: Osaka Japan
  • Year and Date: 20081011-20081015
• [Presentation] DNA methylation analysis in the human brain : promoter tilling array analysis of neuronal and non-neuronal nuclei. (2008)
  • Author(s): Iwamoto K, Bundo M, Ueda J, Nakano Y, Ukai W, Hashimoto E, Saito T, Kato T
  • Organizer: 16th WCPG
  • Place of Presentation: Osaka Japan
  • Year and Date: 20081011-20081015
• [Presentation] 胎児期アルコール曝露モデルに対する神経幹細胞移植の試み (2008)
  • Author(s): 吉永敏弘, 石井貴男, 鵜飼渉, 館農勝, 小野貴文, 渡邊公彦, 渡邉一平, 白坂知彦, 齋藤諭, 橋本恵理, 齋藤利和
  • Organizer: 第18回日本臨床精神神経薬理学会 第38回日本神経精神薬理学会合同年会
  • Place of Presentation: 東京
  • Year and Date: 20081001-20081003
• [Presentation] (Symposium) Neuroprotective effects on atypical antipsychotics against ER stress-induced cell damage. (2008)
  • Author(s): Tateno M, Kurosawa S, Ukai W, Hashimoto E, Ishii T, Yoshinaga T, Saito S. Saito T
  • Organizer: 2nd WFSBP
  • Place of Presentation: Toyama, Japan
  • Year and Date: 20080911-20080913
• [Presentation] (Symposium) translational research of repairing therapy for the damaged brain by ethanol. (2008)
  • Author(s): Ishii T, Yoshinaga T, Ukai W, Hashimoto E, Tateno M, Ono T, Watanabe K, Saito S. Saito T
  • Organizer: 2nd WFSBP
  • Place of Presentation: Toyama, Japan
  • Year and Date: 20080911-20080913
• [Presentation] (Symposium) New potential therapy of neural stem cell transplantation for repairing alcohol-induced brain damage. (2008)
  • Author(s): 齋藤利和, 橋本恵理, 鵜飼渉, 吉永敏弘, 石井貴男, 館農勝, 小野貴文, 渡邊公彦, 齋藤諭
  • Organizer: 16th CINP
  • Place of Presentation: Munich, Germany
  • Year and Date: 20080713-20080717
• [Presentation] Possible new treatment of schizophrenia : A combined therapy of cells and drugs. (2008)
  • Author(s): 鵜飼渉, 橋本恵理, 吉永敏弘, 石井貴男, 館農勝, 小野貴文, 渡邊公彦, 齋藤諭, 齋藤利和
  • Organizer: 16th CINP
  • Place of Presentation: Munich, Germany
  • Year and Date: 20080713-20080717
• [Presentation] (シンポジウム) 精神疾患に対する幹細移植療法の可能性に関する研究 (2008)
  • Author(s): 鵜飼渉, 吉永敏弘, 石井貴男, 橋本恵理, 小野貴文, 館農勝, 渡邉公彦, 渡邉一平, 白坂知彦, 向裕加, 齋藤諭, 齋藤利和
  • Organizer: 第51回日本神経化学会
  • Place of Presentation: 富山
  • Year and Date: 2008-09-12
• [Presentation] 神経細胞および神経幹細胞ダメージに対する外来性神経幹細胞の効果 (2008)
  • Author(s): 小野貴文, 鵜飼渉, 石井貴男, 吉永敏弘, 渡邉公彦, 橋本恵理, 渡邉一平, 白坂知彦, 館農勝, 齋藤諭, 齋藤利和
  • Organizer: 第51回日本神経化学会
  • Place of Presentation: 富山
  • Year and Date: 2008-09-12
• [Remarks] ホームページ等